Translational lung cancer research最新文献

{"title":"Identification of prognostic-related tumor microenvironment genes in lung adenocarcinoma and establishment of a prognostic prediction model.","authors":"Xisheng Fang, Shaopeng Zheng, Zekui Fang, Xiping Wu, Erin L Schenk, Lorenzo Belluomini, Huizhen Fan","doi":"10.21037/tlcr-24-297","DOIUrl":"10.21037/tlcr-24-297","url":null,"abstract":"<p><strong>Background: </strong>With the swift advancements in immunotherapy for solid tumors, exploring immune characteristics of tumors has become increasingly important. The tumor microenvironment (TME) is closely related to the prognosis and treatment of tumor patients. This study aims to explore the expression characteristics and model construction of TME-related genes in lung adenocarcinoma (LUAD) patients, and provide help for clinical diagnosis and treatment.</p><p><strong>Methods: </strong>Through the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm, we analyzed the transcriptomic data of 559 samples from The Cancer Genome Atlas (TCGA) data set to estimate the stromal cells and immune cells, and screened the immune-related differentially expressed genes (DEGs), namely, the TME-DEGs. Essential TME genes were then selected from the TME-DEGs by multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression, and a prediction model of prognostic risk score (RS) was established.</p><p><strong>Results: </strong>We identified 5 crucial TME genes: <i>ABCC2, ECT2L, CD200R1, ACSM5</i>, and <i>CLEC17A</i>. Analysis of the genes' associations with prognosis and clinical features showed that <i>ABCC2</i> was significantly associated with poorer prognosis and decreased immune signatures, whereas the other 4 associated with improved prognosis and immune signatures. Further, a prognostic RS prediction model was constructed based on these 5 genes, and the results showed that patients with low RS had significantly higher overall survival (OS; P<0.001), relapse-free survival (RFS; P=0.009) and disease-free survival (DFS; P=0.005) than the high RS group, and it had a certain predictive accuracy [area under the curve (AUC)] of 5 years OS =0.70). Those were consistent in the GSE50081 cohort.</p><p><strong>Conclusions: </strong>Five crucial TME genes, <i>ABCC2, ECT2L, CD200R1, ACSM5</i>, and <i>CLEC17A</i>, are significantly correlated with the prognosis and tumor immune microenvironment (TIME) characteristic of LUAD patients, and the prognostic model has good prediction efficiency, which may improve clinical prognostic models and therapy selection.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2125-2144"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650656","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":"Response of non-small cell lung cancer harboring different epidermal growth factor receptor mutations to ablative radiotherapy.","authors":"Areej Al Rabea, Ian J Gerard, Paul Daniel, Sophie Camilleri-Broët, Ayman Oweida, Siham Sabri, Bassam Abdulkarim","doi":"10.21037/tlcr-2024-1034","DOIUrl":"10.21037/tlcr-2024-1034","url":null,"abstract":"<p><strong>Background: </strong>Stereotactic ablative radiation therapy (SABR) provides an alternative treatment for patients with inoperable early-stage lung cancer (ES-LC). The epidermal growth factor receptor (<i>EGFR</i>) plays an important role in tumor progression and treatment resistance in non-small cell lung cancer (NSCLC). <i>EGFR</i>-targeted therapies in combination with radiotherapy (RT) have not been successful at enhancing RT's response or improving tumor control. The response of NSCLCs carrying <i>EGFR</i> mutations to SABR has not been well investigated, although worse overall survival is seen among patients with L858R-<i>EGFR</i> mutations. We aim to evaluate the effect of different <i>EGFR</i>-mutant lung cancers to SABR <i>in vitro</i> and <i>in vivo</i> and provide a deeper understanding of the mechanisms of response and resistance to SABR.</p><p><strong>Methods: </strong>A549 cells were stably transfected with either wild-type-<i>EGFR</i> (WT), deleted-<i>EGFR</i> (DEL), or L858R-<i>EGFR</i> (L858R) constructs to generate isogenic cell lines. <i>In vitro</i> assessment included colony formation, cell viability, and proliferation assays. Tumor formation was assessed by subcutaneous injection of pre-irradiated cells in yellow fluorescent protein (YFP)/severe combined immunodeficiency (SCID) mice. All mice were sourced from the Animal Resource Division at the McGill University Healthcare Centre. Response to SABR was evaluated in mice injected subcutaneously with isogenic cells and followed with sham or 34 Gy treatment. Tumors collected from both groups were evaluated for SABR effect histologically.</p><p><strong>Results: </strong><i>EGFR</i>-mutant cell lines displayed a similar <i>in vitro</i> response to SABR: reduced colony formation, cell viability, and cell cycle arrest in G2. Pre-irradiated WT-<i>EGFR</i> and L858R-<i>EGFR</i> NSCLC cell lines maintained their ability to initiate tumor growth <i>in vivo</i>, whilst pre-irradiated DEL-<i>EGFR</i> cells were unable to form tumors upon injection. Subcutaneous DEL-<i>EGFR</i> xenograft tumors had a significant decrease in tumor volume post-SABR treatment compared to WT and L858R-<i>EGFR</i> xenografts. Histological assessment demonstrated less necrosis and a decrease (P=0.049) of apoptotic cells in DEL-<i>EGFR</i>-treated tumors compared to L858R-<i>EGFR</i>.</p><p><strong>Conclusions: </strong>Novel demonstration of DEL-<i>EGFR</i> mutation imparting better response to SABR compared to WT-<i>EGFR</i> or L858R-<i>EGFR</i> mutations, consistent with findings from The Cancer Genome Atlas (TCGA), suggesting L858R-<i>EGFR</i> mutations are associated with worse overall survival. Radiation dose fractionation should be investigated further to establish an optimal SABR regimen in the context of LCs and possible overall survival with <i>EGFR</i> mutations.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2062-2073"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650675","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":"Towards the development of next-generation lung cancer immunotherapy.","authors":"Yoshinobu Ichiki, Nako Saito, Ryo Taguchi, Tetsuya Umesaki, Hiroyuki Nitanda, Hirozo Sakaguchi, Hironori Ishida, Tomonori Kawasaki, Hisao Imai, Kyoichi Kaira, Hiroshi Kagamu","doi":"10.21037/tlcr-2024-1097","DOIUrl":"10.21037/tlcr-2024-1097","url":null,"abstract":"<p><p>The immune system attempts to eliminate foreign substances, such as pathogens and viruses, that invade the body. As normal cells transform into cancerous cells, the immune system can eliminate these cells and suppress cancer onset. The immune system is regulated so that it does not become overactive or attack normal cells. When cancer cells transform from normal cells, they acquire various characteristics, and some cancer cells influence the regulatory function of the immune system to suppress it and escape immune attack. Therefore, treatments have been developed to eliminate the suppression of the immune system by cancer cells and to restore the immune system's ability to eliminate cancer cells. Immunotherapies include immune checkpoint inhibitors, cytokines, cancer vaccines, and effector cell therapies. Cytokine therapy activates the immune system by injecting substances produced by immune cells (such as interleukin 2 and interferon alpha) into the body, thereby increasing the ability of the immune system to attack cancer cells. Cancer vaccine therapy enhances the attack on cancer cells by injecting substances (antigens) that serve as markers for cancer cells into the body to make it easier for immune cells to detect the cancer. Depending on the type of antigen, cancer peptides, tumor cells, and dendritic cell vaccines are available. Effector cell therapy is a treatment method in which immune cells that directly attack cancer cells [CD8⁺ T cells, natural killer (NK) cells, etc.] are taken from the patient's body, expanded outside the body, activated, and returned to the body to attack cancer cells. To develop these treatments, it is essential to understand the cells and molecules related to immunity as well as the local tumor environment. In this article, we consider the factors related to antitumor immunity.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2257-2271"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650680","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":"Comorbidity of lung cancer and chronic obstructive pulmonary disease: correlation and optimization of treatment strategies.","authors":"Huixin Jiang, Gengda Huang, Du Feng, Till Plönes, Robert P Young, Ramin Salehi-Rad, Qibo Liu, Ying Meng, Chengzhi Zhou","doi":"10.21037/tlcr-2025-480","DOIUrl":"10.21037/tlcr-2025-480","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are two major global public health challenges, both characterized by high incidence and mortality rates. Given that COPD and LC share many common risk factors, they frequently coexist, further exacerbating the overall disease burden. The comorbidity of COPD and LC not only increases the risk of both conditions, but also reflects the complex pathophysiological relationship between them. This relationship involves mechanisms such as oxidative stress, chronic inflammation, immune dysregulation, and cellular senescence, which collectively contribute to the development of LC and the progression of COPD. Recent studies have shown that patients with COPD are significantly more likely to develop LC, while the presence of LC may also worsen COPD symptoms and accelerate its progression. This dual impact not only places an additional physiological burden on patients but also complicates the clinical management of these diseases. This study sought to summarize the epidemiological characteristics, comorbidity mechanisms, and key risk factors associated with COPD and LC. It also aimed to explore the shared pathophysiological mechanisms underlying both diseases, highlighting the complex and multifaceted nature of their comorbidity. Additionally, it sought to summarize individualized intervention strategies to reduce the reciprocal impact of both conditions, improve patients' quality of life, and provide scientific evidence for clinical practice, ultimately offering more effective solutions to the growing healthcare challenges posed by this comorbidity.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2296-2308"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650636","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":"Impact of mutant protein expression on clinical outcomes in patients with EGFR L858R-mutated non-small cell lung cancer.","authors":"Ryota Nakamura, Tadaaki Yamada, Kenji Morimoto, Akihiro Yoshimura, Shinsuke Shiotsu, Nozomu Motono, Hidetaka Uramoto, Tatsuya Imabayashi, Yoshizumi Takemura, Yuki Katayama, Naoya Nishioka, Masahiro Iwasaku, Shinsaku Tokuda, Satoru Okada, Masanori Shimomura, Masayoshi Inoue, Noriyuki Tanaka, Aya Miyagawa-Hayashino, Koichi Takayama","doi":"10.21037/tlcr-2025-126","DOIUrl":"10.21037/tlcr-2025-126","url":null,"abstract":"<p><strong>Background: </strong>Currently, patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) are typically treated with osimertinib monotherapy. However, in some patients, the therapeutic efficacy of osimertinib is suboptimal, leading to heterogeneity in treatment response, which presents a clinical challenge. It remains unclear how the expression level of EGFR-mutant protein affects osimertinib treatment and clinical outcomes. In this study, we aimed to examine the association between the expression level of EGFR L858R-mutant protein (EGFR^L858R) and the efficacy of osimertinib by performing immunohistochemical staining of surgical specimens.</p><p><strong>Methods: </strong>We retrospectively assessed consecutive patients with postoperative recurrent EGFR L858R-mutated NSCLC who received osimertinib monotherapy at five hospitals in Japan between September 2018 and February 2022.</p><p><strong>Results: </strong>In total, we analyzed 23 patients with postoperative recurrent EGFR L858R-mutated NSCLC. There were no significant differences in objective response rate, progression-free survival, or overall survival for osimertinib monotherapy between the high and low EGFR^L858R-expressing groups. In contrast, high EGFR^L858R expression was associated with shorter disease-free survival (DFS) than low EGFR^L858R expression (log-rank test P=0.008). Furthermore, EGFR^L858R expression was positively correlated with the percentage of Ki-67-positive cells in tumors (P=0.03).</p><p><strong>Conclusions: </strong>According to our limited data (n=23), the expression level of EGFR^L858R affected only the DFS, with no significant effects on other aspects of survival or treatment efficacy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2001-2010"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650658","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":"Liquid biopsy perspectives in pleomorphic carcinoma of the lung: case report.","authors":"Tania Rossi, Michela Cortesi, Michele Zanoni, Sara Bandini, Camilla Sbrighi, Davide Angeli, Valentina Masciale, Giulia Grisendi, Matteo Costantini, Franco Stella, Paola Ulivi, Beatrice Aramini","doi":"10.21037/tlcr-2024-1275","DOIUrl":"10.21037/tlcr-2024-1275","url":null,"abstract":"<p><strong>Background: </strong>Liquid biopsy has recently made it possible to use minimally invasive testing to examine tumor-derived material released into peripheral blood, including circulating tumor cells (CTCs), extracellular vesicles (EVs), and circulating tumor deoxyribonucleic acid (ctDNA). Lung pleomorphic carcinoma (PC) is an extremely rare and severe form of cancer. Although resection tissues are the basis for PC diagnosis in everyday practice, tiny biopsies and cytologic specimens might potentially raise suspicions. Because PC may show varied expression of conventional carcinoma markers, it can be particularly challenging to differentiate sarcomatoid (i.e., spindle cell or giant cell) components from other tumor forms, such as sarcomatoid mesothelioma and other sarcomas. We think that defining a more specific context to better understand patient prognosis may be aided by the discovery of blood molecular markers in PC.</p><p><strong>Cases description: </strong>We present two cases of patients underwent major lung resection at our center with a diagnosis of PC of the lung; specifically, according with 8th TNM edition, case 1 showed a final pathological stage pathological tumor-node-metastasis (pTNM): pT1cN0G3LV0R0, and case 2 showed a stage pTNM: pT3N0G3LV0R0. Patients were both discharged after surgery with no postoperative complications. Oncologists suggested a 5-year clinical and radiological follow-up, however case 1 patient is free from recurrence at the moment, while case 2 patient died for brain recurrence 10 months after surgery. Immediately after surgical resection, patient's specimens were sent to the pathology unit. The pathologist, without affecting the accuracy of histological diagnosis, selected representative tissue samples and sent them at 4 ℃ in specific media, to Bioscience Laboratory, IRCCS IRST \"Dino Amadori\" for tissue analysis. Additionally, blood samples collected before surgery were sent for the characterization of CTCs and EVs.</p><p><strong>Conclusions: </strong>To better characterize the potential relationship between the presence of CTCs, EVs and high grade of malignancy and any subsequent connection to death and/or recurrence, we think that liquid biopsy, which involves the identification and characterization of tumor-derived elements, may serve as future approach and tool not only in NSCLC but also in each specific histotype as for lung PC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2324-2336"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650659","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":"Monitoring pembrolizumab response in patients with metastatic non-small cell lung cancer using circulating tumour DNA and circulating tumour cells.","authors":"Andrea C Kakouri, Maria Spiliotaki, Eleni M Loizidou, Ioannis Stylianou, Elisavet Papageorgiou, Christina G Panayi, Andreas I Constantinou, Haris Charalambous, Constantinos Deltas, Gregory Papagregoriou","doi":"10.21037/tlcr-2024-1095","DOIUrl":"10.21037/tlcr-2024-1095","url":null,"abstract":"<p><strong>Background: </strong>Liquid biopsy, in the form of cell-free-DNA (cfDNA), circulating-tumour-DNA (ctDNA), and circulating tumour cells (CTCs) can be used to monitor the efficacy of systemic therapy. We investigated the predictive value of these markers in patients with advanced non-small cell lung cancer (aNSCLC) treated with pembrolizumab within a prospective phase-II maintenance study of pembrolizumab post-platinum-doublet-chemotherapy (NCT02705820).</p><p><strong>Methods: </strong>Plasma-derived cfDNA was evaluated in 125 patients' plasma samples at baseline (t0), after 3 weeks (t1), 6 weeks (t2) and 9 weeks (t3) from 46 individuals and analysed by next-generation sequencing to identify and quantify somatic mutations. CTCs were detected in peripheral blood mononuclear cells and characterised according to programme death-ligand 1 (PD-L1) and Ki67.</p><p><strong>Results: </strong>Patients presenting cfDNA increase at t2 had shorter progression-free survival (PFS; 2.05 <i>vs</i>. 6.1 months, P=0.04) and overall survival (OS; 8.35 <i>vs</i>. 20.0 months, P=0.004) than those with decreased cfDNA. Somatic mutations were found in 58.14% of patients in <i>TP53</i>, <i>EGFR</i>, <i>KRAS</i>, <i>ALK</i>, <i>PI3KCA</i> and <i>MAP2K1</i> genes. Patients with >50% decrease or clearance in ctDNA from baseline to early treatment had 3.34 times lower risk for progression and improved survival outcomes (P=0.03). A high Ki67 CTC-index negatively affected PFS [hazard ratio (HR) =10.13, P=0.03] and OS (HR =6.1, P=0.01). Combining ctDNA dynamics and Ki67 was superior to any single marker in identifying patients with disease progression, with a sensitivity of 88.2% at t0 and 70% at t2 and a false-positive rate of 30.4% at t0 and 11.1% at t2.</p><p><strong>Conclusions: </strong>Monitoring ctDNA mutation dynamics during early treatment could serve as a promising real-time predictor of response. Moreover, combining ctDNA-dynamics with Ki67 provides enhanced predictive accuracy for progression, supporting the importance of more holistic multifactorial analyses in the prediction of immunotherapy response in aNSCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"1945-1960"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650661","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":"Natural course of lung adenocarcinoma manifesting as ground-glass nodules: invasiveness assessment based on growth evaluation.","authors":"Yuanhui Wei, Zhen Yang, Zirui Wang, Jiabo Ren, Yue Yin, Shangshu Liu, Xiaoyan Su, Sara Ricciardi, Takehiro Izumo, Wei Zhao, Liang-An Chen","doi":"10.21037/tlcr-2025-395","DOIUrl":"10.21037/tlcr-2025-395","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Investigating the growth characteristics of lung adenocarcinoma manifesting as ground-glass nodules (gLUAD) and assessing its invasiveness based on these features are crucial for optimizing follow-up and intervention strategies. This study aimed to systematically analyze the growth dynamics of gLUAD and compare the value of different growth evaluation methods in predicting gLUAD invasiveness.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 564 participants with 625 gLUAD were retrospectively enrolled from the First and Fourth Medical Centers of the Chinese PLA General Hospital between January 2018 and December 2022. gLUAD was pathologically classified into two categories: adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). Growth evaluation was conducted using four definitions (size growth, volume growth, mass growth, and stage shift) and two growth models (linear and exponential models). These methods were further evaluated in terms of their effectiveness in assessing gLUAD invasiveness.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The median follow-up period of gLUAD in this study was 1,050 days. The median doubling times for total/solid size, volume, and mass of gLUAD were &gt;3,650/3,042 days, 1,460/1,014 days, and 1,521/1,014 days, respectively. For AIS/MIA, all doubling times exceeded 3,650 days, whereas for IAC, they were 3,318/2,147 days, 1,141/777 days, and 1,074/760 days, respectively. The R&lt;sup&gt;2&lt;/sup&gt; and root mean squared error (RMSE) values for the linear and exponential growth models in fitting total/solid size, volume, and mass were 0.98/0.95 &lt;i&gt;vs.&lt;/i&gt; 0.98/0.95, 0.98/0.90 &lt;i&gt;vs.&lt;/i&gt; 0.98/0.93, and 0.95/0.90 &lt;i&gt;vs.&lt;/i&gt; 0.98/0.92 for R&lt;sup&gt;2&lt;/sup&gt;, while they were 0.53/0.92 &lt;i&gt;vs.&lt;/i&gt; 0.51/0.94, 169.80/100.00 &lt;i&gt;vs.&lt;/i&gt; 143.87/106.81, and 116.12/101.24 &lt;i&gt;vs.&lt;/i&gt; 72.81/108.99 for RMSE, respectively. The median growth times for size growth, volume growth, mass growth, and stage shift of gLUAD were 1,273, 750, 792, and 1,672 days, respectively. Compared to AIS/MIA, IAC exhibited significantly higher growth rates (all P values &lt;0.001). For invasiveness assessment, the linear growth rates (LGRs) outperformed the exponential growth rates (EGRs) in discriminative value (all P values &lt;0.05). Among the growth evaluation methods, the LGR of total mass demonstrated the highest discriminative ability for pathological subtypes of gLUAD, with an area under the curve (AUC) of 0.83. At an optimal cutoff of 16.80 mg/year, the accuracy, sensitivity, and specificity for distinguishing gLUAD with different invasiveness were 0.78, 0.77, and 0.79, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;gLUAD exhibited an indolent growth pattern, with significant differences in growth trends between AIS/MIA and IAC. Both the linear and exponential growth models showed similar fitting performance for gLUAD growth, while the linear growth model provided a more reliable assessment of invasiveness. T","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2180-2196"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650668","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":"Efficacy of immunotherapy in advanced <i>ALK</i>-rearranged non-small cell lung cancer patients with disease progression on ALK-TKIs.","authors":"Danni Wang, Yujing Li, Beibei Liu, Yuqing Lou, Lele Zhang, Yueran Sun, Fangfei Qian, Jun Lu, Fusheng Li, Edyta M Urbanska, Diego Kauffmann-Guerrero, Xinwei Wu, Baohui Han, Yanwei Zhang, Wei Zhang","doi":"10.21037/tlcr-2025-505","DOIUrl":"10.21037/tlcr-2025-505","url":null,"abstract":"<p><strong>Background: </strong>Treatment of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (<i>ALK</i>) rearranged non-small cell lung cancer (NSCLC) remains an unmet need. Among these patients, the efficacy of immunotherapy has not been thoroughly investigated. The purpose of our study was to evaluate the efficacy of immunotherapy in patients with ALK-TKI-resistant NSCLC, stratified by programmed cell death ligand-1 (PD-L1) expression.</p><p><strong>Methods: </strong>We retrospectively collected the data of advanced NSCLC patients with <i>ALK</i>-rearrangement, who were treated with immunotherapy or chemotherapy after the development of ALK-TKI resistance at the Shanghai Chest Hospital. Progression-free survival (PFS) was used to evaluate the outcomes.</p><p><strong>Results: </strong>The final analysis included 89 patients between June 1, 2018, and December 31, 2022, who met the selection criteria. The entire cohort had a median follow-up time of 33.4 months. The patients who received immunotherapy had better PFS than those who received non-immunotherapy (median PFS: 5.3 <i>vs.</i> 2.5 months; P=0.009). The PD-L1-positive patients who received immunotherapy had a median PFS of 7.1 months, while those who received non-immunotherapy had a median PFS of 2.5 months (P=0.02). No such statistically significant difference was observed in the PD-L1-negative patients (median PFS for with immunotherapy <i>vs.</i> without immunotherapy: 1.5 <i>vs.</i> 2.9 months; P=0.68). The PD-L1-positive patients who underwent re-biopsy after the development of TKI resistance and who received immunotherapy had a PFS of 7.8 months, while those who received non-immunotherapy had a PFS of 2.7 months (P=0.002).</p><p><strong>Conclusions: </strong>This was the first real-world retrospective study to show that some patients with positive PD-L1 expression may benefit from immune-based therapy after the development of ALK-TKI resistance. However, we still recommend biopsy for patients who develop ALK-TKI resistance to provide further treatment guidance.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2197-2209"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650640","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 growth prediction models for multiple pulmonary ground-glass nodules based on CT features, radiomics, and deep learning.","authors":"Shulei Cui, Linlin Qi, Weixiong Tan, Yujian Wang, Fenglan Li, Jianing Liu, Jiaqi Chen, Sainan Cheng, Zhen Zhou, Jianwei Wang","doi":"10.21037/tlcr-24-1039","DOIUrl":"10.21037/tlcr-24-1039","url":null,"abstract":"<p><strong>Background: </strong>The development of growth prediction models for multiple pulmonary ground-glass nodules (GGNs) could help predict their growth patterns and facilitate more precise identification of nodules that require close monitoring or early intervention. Previous studies have demonstrated the indolent growth pattern of GGNs and developed growth prediction models; however, these investigations predominantly focused on solitary GGN. This study aimed to investigate the natural history of multiple pulmonary GGNs and develop and validate growth prediction models based on computed tomography (CT) features, radiomics, and deep learning (DL) as well as compare their predictive performances.</p><p><strong>Methods: </strong>Patients with two or more persistent GGNs who underwent CT scans between October 2010 and November 2023 and had at least 3 years of follow-up without radiotherapy, chemotherapy, or surgery were retrospectively reviewed. The growth of GGN is defined as an increase in mean diameter by at least 2 mm, an increase in volume by at least 30%, or the emergence or enlargement of a solid component by at least 2 mm. Based on the interval changes during follow-up, the enrolled patients and GGNs were categorized into growth and non-growth groups. The data were randomly divided into a training set and a validation set at a ratio of 7:3. Clinical model, Radiomics model, DL model, Clinical-Radiomics model, and Clinical-DL model were constructed. Model performance was assessed using the area under the receiver operating characteristic curve (AUC).</p><p><strong>Results: </strong>A total of 732 GGNs [mean diameter (interquartile range, IQR), 5.5 (4.5-6.5) mm] from 231 patients (mean age 54.1±9.9 years; 26.4% male, 73.6% female) were included. Of the 156 (156/231, 67.5%) patients with GGN growth, the fastest-growing GGN had a volume doubling time (VDT) and mass doubling time (MDT) of 2,285 (IQR, 1,369-3,545) and 2,438 (IQR, 1,361-4,140) days, respectively. Among the growing 272 (272/732, 37.2%) GGNs, the median VDT and MDT were 2,934 (IQR, 1,648-4,491) and 2,875 (IQR, 1,619-5,148) days, respectively. Lobulation (P=0.049), vacuole (P=0.009), initial volume (P=0.01), and mass (P=0.01) were risk factors of GGN growth. The sensitivity and specificity of the Clinical model 1, Clinical model 2, Radiomics, DL, Clinical-Radiomics, and Clinical-DL models were 77.2% and 80.0%, 77.2% and 79.3%, 75.9% and 77.8%, 59.5% and 75.6%, 82.3% and 86.7%, 78.5% and 80.7%, respectively. The AUC for Clinical model 1, Clinical model 2, Radiomics, DL, Clinical-Radiomics, and Clinical-DL models were 0.876, 0.869, 0.845, 0.735, 0.908, and 0.887, respectively.</p><p><strong>Conclusions: </strong>Multiple pulmonary GGNs exhibit indolent biological behaviour. The Clinical-Radiomics model demonstrated superior accuracy in predicting the growth of multiple GGNs compared to Clinical, Radiomics, DL, Clinical-DL models.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"1929-1944"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650638","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}