Translational lung cancer research最新文献

{"title":"Neoadjuvant or conversion anti-PD-1/PD-L1 immunotherapy combined with chemotherapy improves 2-year survival and achieves high pathological complete response rate in patients with stage IIB-IIIB small-cell lung cancer.","authors":"Zhiyuan Gao, Zhengxuan Li, Xin Yao, Changjian Shao, Jia Chen, Zenghui Fan, Jinbo Zhao, Jian Wang, Yunfeng Ni, Mingliang Xing, Xiaolong Yan","doi":"10.21037/tlcr-2025-1-1496","DOIUrl":"https://doi.org/10.21037/tlcr-2025-1-1496","url":null,"abstract":"<p><strong>Background: </strong>Limited-stage small-cell lung cancer (LS-SCLC) is an aggressive malignancy, and patients with this disease have a poor long-term survival when treated with current standard chemoradiotherapy. Although neoadjuvant or conversion immunotherapy combined with chemotherapy has shown efficacy in patients with non-SCLC (NSCLC), its effect in those with LS-SCLC remains underexplored, particularly regarding long-term survival outcomes. This study aims to evaluate the efficacy and long-term survival of neoadjuvant or conversion immunotherapy plus chemotherapy in patients with LS-SCLC.</p><p><strong>Methods: </strong>This retrospective study enrolled 34 patients with stage IIB-IIIB SCLC who received neoadjuvant or conversion anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy plus platinum-etoposide chemotherapy, followed by surgical resection. The primary end points were overall survival (OS) and event-free survival (EFS). Pathological complete response (pCR) and major pathological response (MPR) were assessed, and subgroup analyses were performed based on pathological response, demographic factors, and tumor stage.</p><p><strong>Results: </strong>With a median follow-up of 34.2 months, the 2-year EFS and OS rates were 72.1% [95% confidence interval (CI): 53.1-84.5%] and 82.4% (95% CI: 64.9-91.7%), respectively. Among the 34 patients, a pCR rate of 47.1% and an MPR rate of 70.6% were achieved. Patients achieving pCR or MPR had significantly better survival outcomes than did the nonresponders. In the subgroup analysis, a lower body mass index (BMI) (<25.0 kg/m²) and earlier disease stage II were associated with improved survival, although this was not statistically significant in all comparisons.</p><p><strong>Conclusions: </strong>Neoadjuvant or conversion chemoimmunotherapy followed by surgery demonstrates promising efficacy and survival benefits in patients with stage IIB-IIIB SCLC, with high pCR/MPR rates strongly predicting superior outcomes. These findings support the integration of immunotherapy into multimodal treatment strategies for patients with stage II-IIIB SCLC and warrant validation in larger randomized controlled trials.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"60"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692261","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 impact of thyroid transcription factor-1 expression and the efficacy of carboplatin plus (nab-) paclitaxel in non-squamous non-small cell lung cancer complicated with idiopathic interstitial pneumonias.","authors":"Yuto Terashima, Aya Fukuizumi, Koichiro Kamio, Iori Abe, Erika Miyake, Keiki Miyadera, Yasuhiro Kato, Kakeru Hisakane, Shinji Nakamichi, Susumu Takeuchi, Akihiko Miyanaga, Yasuhiro Terasaki, Kazuo Kasahara, Masahiro Seike","doi":"10.21037/tlcr-2025-1-1367","DOIUrl":"https://doi.org/10.21037/tlcr-2025-1-1367","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have reported an association between expression of thyroid transcription factor 1 (TTF-1) and the efficacy of immune checkpoint inhibitors (ICIs), cytotoxic chemotherapy, and immunochemotherapy in patients with advanced non-squamous non-small cell lung cancer (NS-NSCLC). However, the relationship between TTF-1 expression and the efficacy of cytotoxic chemotherapy in patients with NS-NSCLC with idiopathic interstitial pneumonias (IIPs) remains unclear. This study aimed to evaluate the relationship TTF-1 expression and the efficacy of platinum-doublet chemotherapy in patients with NS-NSCLC with coexisting IIPs.</p><p><strong>Methods: </strong>This retrospective study reviewed 120 patients with NSCLC complicated by IIPs who were treated at Nippon Medical School Hospital in Japan between January 2010 and December 2024. We analyzed the efficacy and safety of carboplatin and either paclitaxel or nanoparticle albumin-bound (nab-) paclitaxel for NS-NSCLC with IIPs.</p><p><strong>Results: </strong>In the total cohort, 51 patients were evaluated for TTF-1 expression status and administered carboplatin plus (nab-) paclitaxel as first-line therapy. TTF-1 expression was observed in 32 patients (63%). Twenty-five patients (49%) exhibited a usual interstitial pneumonia (UIP) pattern. The overall response rate (ORR) was significantly higher in the TTF-1-positive group compared to the TTF-1-negative group (62.4% <i>vs.</i> 31.6%, P=0.045). Median overall survival (OS) and progression-free survival (PFS) were also significantly longer in the TTF-1-positive group than in TTF-1-negative group (11.3 <i>vs.</i> 8.2 months, P=0.007; 8.4 <i>vs.</i> 4.4 months, P<0.001). TTF-1 negativity was identified as an independent prognostic factor associated with inferior OS and PFS in multivariate analysis. Furthermore, the TTF-1-negative group had a significantly higher incidence of lung cancer development in the setting of underlying interstitial pneumonia (IP) (P<0.001), suggesting that decreased TTF-1 expression may be involved in the pathogenesis of lung cancer arising from IIPs.</p><p><strong>Conclusions: </strong>TTF-1 expression is an independent prognostic factor in patients with NS-NSCLC complicated by IIPs who received carboplatin plus (nab-) paclitaxel. TTF-1 expression may represent a valuable biomarker for characterizing the disease subtypes and guiding therapeutic strategies in lung cancer with coexisting IIPs.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"54"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692306","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":"The 2025 lung cancer landscape: advances in screening, molecular taxonomy and therapeutic strategy: a narrative review.","authors":"Wenhai Fu, Xusen Zou, Tianrui He, Qi Cai, Peiling Chen, Bo Cheng, Yi Feng, Caichen Li, Feng Li, Jianfu Li, Huiting Wang, Shan Xiong, Wenjun Ye, Xin Zheng, Jianxing He, Wenhua Liang","doi":"10.21037/tlcr-2025-1-1477","DOIUrl":"https://doi.org/10.21037/tlcr-2025-1-1477","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;In 2025, lung cancer research advanced rapidly across the disease continuum, from population-level risk assessment and screening to mechanistic studies of early carcinogenesis and therapeutic innovation in perioperative and metastatic settings. A key shift moved beyond a smoking-centred paradigm toward a multidimensional risk framework reflecting the growing burden among never-smokers and the roles of air pollution, occupational exposures, and systemic metabolic-inflammatory states. This narrative review aims to synthesize influential 2025 evidence across prevention, diagnosis, treatment, and survivorship, and to identify convergent themes and translational gaps relevant to clinical practice and policy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed a narrative synthesis of influential lung cancer studies published in major international journals in 2025. Evidence was organized along a clinically oriented pathway spanning carcinogenesis and screening, precision diagnosis, treatment optimization in resectable and advanced disease, and survivorship, emphasizing practice-informing trials, high-impact translational research, and implementation-relevant technologies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key content and findings: &lt;/strong&gt;Lineage tracing, single-cell and spatial omics, and evolutionary inference refined concepts of field cancerization, clonal selection, and copy-number-driven fitness. In small-cell lung cancer, evidence further supported neuronal coupling and synapse-like programs as potentially tractable vulnerabilities. Clinically, low-dose computed tomography (CT) strategies and data-informed nodule thresholds aimed to balance under-detection against over-surveillance harms. In diagnostics, artificial intelligence (AI) models increasingly inferred molecular features from routine histopathology (\"virtual molecular testing\") and should be regarded as decision support requiring prospective validation, population calibration, and explicit failure-mode reporting. Multimodal approaches integrating imaging with circulating tumor DNA (ctDNA) improved feasibility in tissue-limited settings, but clinical utility remains contingent on assay standardization and pathway-level implementation. In resectable disease, longer follow-up consolidated neoadjuvant chemo-immunotherapy for selected patients, while ctDNA kinetics emerged as a candidate biomarker for response-adaptive escalation and de-escalation. In advanced non-small cell lung cancer (NSCLC), phase III evidence for antibody-drug conjugates and bispecific antibodies began reshaping sequencing, while highlighting challenges in toxicity, access, affordability, and immature overall survival in several programs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The 2025 landscape reflects coordinated progress in risk conceptualization, biology, diagnostics, and therapeutics, yet gaps in validation, standardization, and real-world deliverability persist. Priorities include prospective eva","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"62"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692437","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":"Retrospective study of alectinib treatment among variants of <i>ALK</i> fusion in lung adenocarcinoma.","authors":"Yuma Watanabe, Ayako Takigami, Shu Hisata, Masayuki Nakayama, Naoko Mato, Makoto Maemondo","doi":"10.21037/tlcr-2025-aw-1224","DOIUrl":"https://doi.org/10.21037/tlcr-2025-aw-1224","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic lymphoma kinase (<i>ALK</i>) fusion genes are present in approximately 3-5% of non-small cell lung cancer (NSCLC) cases. Multiple echinoderm microtubule-associated protein-like 4-<i>ALK</i> (<i>EML4-ALK</i>) fusion variants have been identified, with variants 1-3 (V1-3) accounting for approximately 90% of cases. However, clinical data on the efficacy of alectinib across these variants remain limited. In this study, we retrospectively evaluated the efficacy of alectinib treatment among <i>ALK</i>-fusion variants.</p><p><strong>Methods: </strong>We performed a retrospective analysis of patients treated with alectinib between January 2019 and December 2024. <i>ALK</i>-fusion variants were identified using Mutation Investigator using Next-era Sequencer (MINtS), a next-generation sequencing-based multigene mutation search system. Progression-free survival (PFS), response rate, and overall survival (OS) were evaluated.</p><p><strong>Results: </strong>A total of 11 patients (male: n=4, female: n=7) were enrolled (V1: n=4, V2: n=3, V3: n=4); their median age was 75 years. Clinical stages at diagnosis were: stage II (n=1), and stage IV (n=10). Intrapulmonary metastasis was common in patients with V3. The median maximum tumor reduction rates were 90.5% (range, 84.0-92.0%), 63.4% (range, 35.0-84.0%), and 98.0% (range, 67.8-100.0%) for patients with V1, V2, and V3, respectively. The best overall response was partial response (PR) in all patients with V1 and V2. Three patients with V3 had complete response (CR) and one had PR. The median PFS was 16.5 and 15.9 months for patients with V1 and V2, respectively, and not reached for those with V3.</p><p><strong>Conclusions: </strong>In this study, there was no significant difference in the therapeutic effect of alectinib by <i>ALK</i> fusion variants. This finding indicates that alectinib may be an effective treatment option even for patients with V3.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"56"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692448","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":"Development and validation of a habitat-based computed tomography radiomics model for differentiating isolated lung cancer, isolated tuberculoma, and coexistence of tuberculosis with lung cancer: a dual-center retrospective study.","authors":"Ning Shi, Zhenzhen Wan, Limin Wen, Zhenpeng Liu, Bing Wang, Ye Li, Peng Xiong, Dailun Hou, Xiuling Liu","doi":"10.21037/tlcr-2025-1-1381","DOIUrl":"https://doi.org/10.21037/tlcr-2025-1-1381","url":null,"abstract":"<p><strong>Background: </strong>Isolated lung cancer (ILC), isolated tuberculoma, and coexistence of tuberculosis with lung cancer (CTBLC) exhibit similarities in computed tomography (CT) imaging features but great differences in pathology, treatment strategy, and prognosis; therefore, accurate differential diagnosis is critical for clinical management and patient safety. The purpose of this study was to develop and validate a habitat-based CT radiomics model that integrates intralesional subregion features with whole-lesion features for reliable differentiation among these three conditions.</p><p><strong>Methods: </strong>This study retrospectively included 317 patients with ILC, tuberculoma, or CTBLC from 2018 to 2022. Among these, 239 patients from Beijing Chest Hospital, Capital Medical University (Center 1) formed the training and internal test cohorts, and 78 from Infectious Disease Hospital of Heilongjiang Province (Center 2) constituted an external validation cohort. Volumes of interest (VOIs) were manually outlined by two experienced radiologists on CT images. Then each lesion was partitioned into two subregions using K-means clustering. A total of 1,218 three-dimensional whole-lesion radiomics features and 2,436 habitat features were extracted. Feature selection was performed via least absolute shrinkage and selection operator (LASSO). Six classification algorithms were trained and evaluated. To distinguish ILC, tuberculoma, and CTBLC, three models were developed: (I) a traditional radiomics model using only whole-lesion radiomics features; (II) a habitat model based on intralesional habitat features; and (III) a combined habitat-radiomics model fusing both feature sets. Discrimination was assessed using the area under the curve (AUC), and SHapley Additive exPlanations (SHAP) was used to interpret the optimal model and visualize individual prediction decisions.</p><p><strong>Results: </strong>The combined habitat-radiomics model that integrates habitat and whole-lesion features outperformed the traditional radiomics model. Among them, the extreme gradient boosting (XGBoost)-based fusion model achieved the best performance (mean AUC =0.934) in the internal test cohort, surpassing both the radiomics model (mean AUC =0.910) and the habitat model (mean AUC =0.873). For individual classes, the fusion model yielded AUCs of 0.911 (ILC), 0.955 (tuberculoma), and 0.937 (CTBLC). Compared with the interpretations provided by three radiologists, the combined radiomics-habitat model demonstrated better discriminative performance. SHAP plots revealed key features and presented individual visualizations of each prediction.</p><p><strong>Conclusions: </strong>A habitat-based CT radiomics approach that incorporates intralesional subregion features into whole-lesion signatures improves differentiation among ILC, tuberculoma, and CTBLC. This combined model provides a noninvasive tool to support clinical decision-making.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"49"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692018","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":"NOTCH4 as a driver of epithelial-mesenchymal transition, angiogenesis, and stromal remodeling in lung adenocarcinoma: integrated transcriptomic and protein-level validation.","authors":"Young Wha Koh, Jae-Ho Han, Seokjin Haam, Hyun Woo Lee","doi":"10.21037/tlcr-2025-1015","DOIUrl":"https://doi.org/10.21037/tlcr-2025-1015","url":null,"abstract":"<p><strong>Background: </strong>Although NOTCH4 plays an important role in tumor progression, its role in lung adenocarcinoma (LUAD) remains unclear. We examined the role of NOTCH4 in LUAD progression, its influence on the tumor microenvironment (TME), and its prognostic value, while isolating its specific contribution from those of NOTCH1 and NOTCH3.</p><p><strong>Methods: </strong>Gene set enrichment analysis (GSEA) and deconvolution-based TME analyses (xCell, ESTIMATE, and MCP-counter) were performed using three independent LUAD cohorts [The Cancer Genome Atlas (TCGA), OncoSG, and CPTAC]. Associations between NOTCH4 expression and epithelial-mesenchymal transition (EMT), angiogenesis, stromal remodeling, and survival were further validated using immunohistochemistry and histopathology in an independent LUAD cohort (n=347).</p><p><strong>Results: </strong>GSEA revealed significant enrichment of the EMT pathway in NOTCH4-high tumors across all three mRNA datasets. Deconvolution analyses demonstrated that NOTCH4-high tumors exhibited increased numbers of endothelial cells, fibroblasts, pericytes, and higher stromal and microenvironment scores, particularly in TCGA and OncoSG cohorts. In CPTAC, NOTCH4-high tumors showed enrichment of endothelial and fibroblast signatures, although global stromal and immune scores were not significantly different. In the independent cohort, after adjusting for NOTCH1 and NOTCH3 levels as covariates, NOTCH4 remained significantly associated with vimentin (Rho =0.160, P=0.007), microvessel density (MVD) (Rho =0.279, P<0.001), and stromal proportion (Rho =0.274, P<0.001), confirming its independent correlation with these markers. High NOTCH4 expression at both the mRNA and protein levels was associated with poorer overall survival (P=0.009 and P=0.009, respectively).</p><p><strong>Conclusions: </strong>Our findings provide the first systematic evidence that NOTCH4 is associated with EMT, angiogenesis, and stromal remodeling in LUAD, independent of NOTCH1 and NOTCH3 expression. By validating these associations at the protein level in an independent cohort, we highlight the translational potential of NOTCH4 as a prognostic biomarker and therapeutic target.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"55"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692294","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":"B cell-driven refractory hemocytopenia in immune checkpoint inhibitor therapy: a report of two cases.","authors":"Feng Li, Chunyan Wang, Guohua Yao, Shaotong Zhang, Qian Hu, Zhenyu Ju, Wenhua Liang","doi":"10.21037/tlcr-2025-939","DOIUrl":"https://doi.org/10.21037/tlcr-2025-939","url":null,"abstract":"<p><strong>Background: </strong>The integration of immune checkpoint inhibitors (ICIs) with chemotherapy has revolutionized lung cancer treatment, yet it amplifies the risk of severe hematologic toxicities.</p><p><strong>Case description: </strong>We describe two patients with advanced lung cancer who developed life-threatening refractory hemocytopenia following ICIs-chemotherapy, unresponsive to glucocorticoids and hematopoietic growth factors. A striking feature of these cases was the exclusive presence of anti-Sjögren's-syndrome-related antigen A (Ro) (SSA) antibodies in refractory patients, but absent in non-refractory controls. Targeted administration of intravenous immunoglobulin (IVIG) and rituximab was temporally associated with clearance of anti-SSA antibodies and restoration of normal hematopoiesis, raising the hypothesis that aberrant B cell activity may contribute to refractory hemocytopenia in this setting.</p><p><strong>Conclusions: </strong>These observations suggest that anti-SSA antibodies could represent a candidate biomarker for identifying refractory hemocytopenia in early time. These findings support a proposal for routine anti-SSA screening in ICI-related hematologic toxicity to enable timely B cell-targeted management.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"67"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691973","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":"Advances in the research on radiotherapy for lung cancer: a 2025 review.","authors":"Jiaying Deng, Zhengfei Zhu","doi":"10.21037/tlcr-2026-1-0034","DOIUrl":"https://doi.org/10.21037/tlcr-2026-1-0034","url":null,"abstract":"<p><p>This study reviewed radiotherapy-related studies on lung cancer presented at the 2025 major international conferences [American Society of Clinical Oncology (ASCO), World Conference on Lung Cancer (WCLC), European Society for Medical Oncology (ESMO), and American Society for Radiation Oncology (ASTRO)] or published in high-impact journals. The studies were classified by pathological type [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] and analyzed according to different tumor stages. Research showed that the combination of immunotherapy and stereotactic body radiotherapy (SBRT) failed to improve overall survival (OS) and progression-free survival (PFS) in early-stage NSCLC, so its combined application requires caution. In locally advanced NSCLC, EA5181 and SKYSCRAPER-03 trials identified that durvalumab administered concurrently with definitive chemoradiotherapy (dCRT) or atezolizumab + tiragolumab combination following concurrent chemoradiation therapy (cCRT) failed to improve PFS. The PACIFIC regimen remains the current standard treatment. R-ALPS trial indicated that, as consolidation therapy after dCRT, immunotherapy combined with anti-angiogenic agents achieved a prolongation of PFS with manageable treatment-related adverse events (TRAEs). In advanced NSCLC, NROG-002 and NorthStar trials demonstrated that epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) plus thoracic radiotherapy (TRT) or local consolidation therapy (LCT) can significantly improve patients' PFS. The results expanded the traditional \"oligometastasis\" definition from \"oligo-sites\" to \"oligo-organs\". For SCLC treatment, hypofractionated radiotherapy (HyPORT) has comparable efficacy to conventional radiotherapy, with a lower incidence of adverse reactions. NRG-CC003 trial indicated that hippocampal avoidance prophylactic cranial irradiation (HA-PCI) reduced neurocognitive function (NCF) failure in comparison with PCI. This review provides references for clinical decision-making in lung cancer radiotherapy and future research directions.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"64"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691983","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":"Lightweight hybrid foundation model for lung cancer prognosis based on low-dose chest X-ray images.","authors":"Helen Haile Hayeso, Zenebe Markos Lonseko, Fahad Mushabbab G Alotaibi, Tao Gan, Peifeng Shi, Shuqi Dong, Nini Rao","doi":"10.21037/tlcr-2025-aw-1299","DOIUrl":"https://doi.org/10.21037/tlcr-2025-aw-1299","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer (LC) is the leading cause of cancer mortality worldwide. Accurate prognosis in vulnerable populations, particularly in low-resource settings remains challenging with high radiation dose of standard imaging modalities. While chest X-rays (CXRs) are safer and more accessible, their low spatial resolution limits prognostic accuracy. Existing multimodal models primarily rely on computationally intensive architectures, such as computed tomography (CT) or positron emission tomography (PET) inputs, which reduce their clinical utility. This study aimed to develop and validate a lightweight hybrid foundation model (LHFM) that integrates CXR imaging with clinical data to enable accurate LC prognosis in low-resource settings.</p><p><strong>Methods: </strong>We developed a LHFM that integrates visual features from CXR images extracted by a segment anything model (SAM)-Med2D encoder with semantically enriched prompts generated by BioGPT and clinical metadata. These multimodal features are fused via a dual-branch transformer architecture for survival prediction. The model was trained and validated on the JSRT and PadChest datasets, with external validation on multicenter datasets including the NIH CXR. Performance was evaluated using the concordance index (C-index), area under the receiver operating characteristic curve (AUROC), and Kaplan-Meier (KM) survival analysis.</p><p><strong>Results: </strong>The proposed LHFM achieved superior prognostic performance, with a C-index of 0.910 [95% confidence interval (CI): 0.898-0.922, standard deviation (SD) =0.006] and AUROC of 0.935 (95% CI: 0.927-0.943, SD =0.004), outperforming existing multimodal benchmarks (P<0.001). KM curves demonstrated significant separation between the high-risk and low-risk groups. Domain-shift robustness testing across heterogeneous external datasets demonstrated representation stability under distribution shift.</p><p><strong>Conclusions: </strong>LHFM establishes a new paradigm for prognostic precision by exhibiting significant performance from low-dose CXR. This hybrid approach directly addresses the implementation gap in clinical artificial intelligence (AI), offering a scalable, equitable, and immediately applicable solution for personalized cancer care in resource-limited and radiography first workflows, with potential applicability across other cancer types.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"47"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692302","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":"Molecular and clinical disparity of <i>EGFR</i>-mutant non-small cell lung cancer (NSCLC) based on histopathological stage and <i>EGFR</i> molecular subtypes.","authors":"Dayoung Yoon, Ji Won Lee, Byoung Chul Cho, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Seong Yoon Yi, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Seungtaek Lim, Hyung Soon Park, Jang Ho Cho, Byunghyun Jang, Ji Yoon Lee, Jiwon Kim, Jisoo Hong, Harim Koo, Seok Chung, Sang Won Shin, Yeul Hong Kim, Jason K Sa, Yoon Ji Choi","doi":"10.21037/tlcr-2025-1-1354","DOIUrl":"https://doi.org/10.21037/tlcr-2025-1-1354","url":null,"abstract":"<p><strong>Background: </strong>While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a cornerstone of therapy for advanced <i>EGFR</i>-mutant non-small cell lung cancer (NSCLC), resistance remains a major clinical challenge. The genomic landscape of early-stage (ES) <i>EGFR</i>-mutant NSCLC and its evolution to advanced-stage (AS) disease is not fully understood. This study aimed to characterize the molecular disparities between ES and AS <i>EGFR</i>-mutant NSCLC and to identify genomic alterations associated with EGFR-TKI treatment outcomes.</p><p><strong>Methods: </strong>We have collected and profiled the complex genomes of 121 ES and 74 AS NSCLCs to determine their molecular and clinical disparities. Furthermore, we analyzed 84 <i>EGFR-</i>mutant NSCLC patients who were treated with EGFR-TKIs to identify potential molecular correlates that could predict the treatment response within the clinic. Patients were stratified by progression-free survival (PFS) and overall response rate (ORR), and hazard ratio analyses were performed.</p><p><strong>Results: </strong>In the study, significant enrichment of mutations in <i>MTOR</i>, <i>ATRX</i>, <i>STAG2</i>, <i>ABL1</i>, and <i>SPEN</i> was observed in AS tumors, whereas ES tumors predominantly exhibited mutations activating <i>JAK2</i>, <i>ERBB2</i>, and <i>FGFR4</i>. In the EGFR-TKI cohort, poor responders harbored frequent mutations in <i>TP53</i>, <i>KIT</i>, and <i>ALK</i>, and these were associated with worse clinical outcomes. Conversely, favorable responders showed enrichment of <i>MTOR</i>, <i>ATM</i>, <i>EP300</i>, and <i>PIK3R1</i> mutations. <i>ALK</i> and <i>FANCA</i> were linked to increased hazard, while <i>EP300</i> and <i>PIK3R1</i> mutations correlated with improved prognosis.</p><p><strong>Conclusions: </strong>Given the growing importance of biomarker-driven treatment in the field of oncology, our results collectively open up new therapeutic opportunities for ES NSCLC patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 3","pages":"50"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692289","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}