Lung Cancer最新文献

{"title":"Canadian Perspectives Revisited: Consensus on the management of ALK-rearranged NSCLC","authors":"Barbara Melosky ,&nbsp;Quincy S.C. Chu ,&nbsp;Rosalyn A. Juergens ,&nbsp;Stephanie Snow ,&nbsp;Normand Blais ,&nbsp;Parneet Cheema ,&nbsp;Randeep Sangha ,&nbsp;Jason Agulnik ,&nbsp;Ilidio Martins ,&nbsp;Ronald L. Burkes ,&nbsp;Zia Poonja ,&nbsp;Mark D. Vincent ,&nbsp;Geoffrey Liu","doi":"10.1016/j.lungcan.2025.108717","DOIUrl":"10.1016/j.lungcan.2025.108717","url":null,"abstract":"<div><div>Inhibition of the anaplastic lymphoma kinase (ALK) oncogenic driver in advanced non-small cell lung carcinoma (NSCLC) improves survival. In 2016 and 2018, Canadian thoracic oncology specialists published consensus on the identification and treatment of <em>ALK-</em>rearranged patients, recommending use of first- and second-generation ALK inhibitors, as initial and subsequent treatment in the advanced setting. New scientific literature warrants a consensus update.</div><div>ALK inhibitor pivotal and phase III clinical trials were reviewed to assess benefits, risks, and implications relative to current Canadian guidance for <em>ALK-</em>rearranged NSCLC patients.</div><div>Updated Canadian recommendations for management of <em>ALK-</em>rearranged NSCLC:<ul><li><span>•</span><span><div>Resected patients considered to be at high risk of recurrence (stage IB [tumors ≥ 4 cm] to IIIA) should receive alectinib as the new standard of care for adjuvant treatment.</div></span></li><li><span>•</span><span><div>Patients with treatment-naïve advanced disease should be treated with lorlatinib (preferred), alectinib or brigatinib.</div></span></li><li><span>•</span><span><div>Patients previously-treated with second-generation inhibitors should receive lorlatinib.</div></span></li><li><span>•</span><span><div>Patients progressing on crizotinib can be offered alectinib (preferred), brigatinib (preferred), lorlatinib or ceritinib.</div></span></li><li><span>•</span><span><div>Patients exhausting ALK-directed therapy options should be considered for pemetrexed-based chemotherapy or clinical trials.</div></span></li><li><span>•</span><span><div>Use of immunotherapy regimens is not recommended.</div></span></li><li><span>•</span><span><div>Patients with early and advanced stage NSCLC must undergo molecular testing for <em>ALK</em> rearrangements.</div></span></li></ul>Our consensus recommendations highlight major developments in management of <em>ALK</em>-rearranged NSCLC and their relevance to the Canadian context. We strongly support upfront ALK testing, treatment of high-risk resected patients with adjuvant alectinib, and use of next-generation ALK inhibitors (lorlatinib, alectinib, brigatinib) as initial treatment of advanced patients.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108717"},"PeriodicalIF":4.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in EGFR-mutant NSCLC after TKI resistance: role of mutation subtypes and progression patterns","authors":"Yitian Zhang ,&nbsp;Xiaomeng Dai ,&nbsp;Jinzi Liang ,&nbsp;Chensu Yang ,&nbsp;Chao Wan ,&nbsp;Lei Sun ,&nbsp;Qiang Qiao ,&nbsp;Shuang Li ,&nbsp;Xuanwen Bao ,&nbsp;Xiaoyan Chen ,&nbsp;Luanluan Huang ,&nbsp;Xiaomeng Liu ,&nbsp;Shiping Zhang ,&nbsp;Chunyang Zhou ,&nbsp;Xinhang Gu ,&nbsp;Fangyuan Zhou ,&nbsp;Kunyu Yang ,&nbsp;Lu Wen ,&nbsp;Yanwei Lu ,&nbsp;Haibo Zhang","doi":"10.1016/j.lungcan.2025.108715","DOIUrl":"10.1016/j.lungcan.2025.108715","url":null,"abstract":"<div><h3>Background</h3><div>Patients with<!--> <!-->EGFR-sensitizing mutations in non-small cell lung cancer (NSCLC) predominantly receive first-line tyrosine kinase inhibitors (TKIs). Subsequent TKI resistance manifests through heterogeneous clinicopathological features, including distinct resistance subtypes (primary vs. acquired),<!--> <!-->PD-L1<!--> <!-->expression levels, and molecular profiles from re-biopsies. While immunotherapy represents a potential subsequent option, the predictive biomarkers guiding optimal patient selection remain undefined.</div></div><div><h3>Patients and methods</h3><div>This multicenter retrospective study analyzed 1,396 EGFR-mutant NSCLC patients from five Chinese institutions, with 312 meeting stringent inclusion criteria. Comprehensive treatment data encompassing EGFR-TKIs, platinum-based chemotherapy, anti-angiogenic agents, and immune checkpoint inhibitors (ICIs) were collected. Cox proportional hazards regression identified progression-free survival (PFS)-associated variables, enabling resistance subtyping. Comparative effectiveness analyses across therapeutic modalities were performed.</div></div><div><h3>Results</h3><div>Multivariable Cox regression identified two independent predictors of immunotherapy PFS:<!--> <!-->EGFR<!--> <!-->mutation subtypes (exon21 L858R vs. exon19del; HR 0.84, 95 % CI [0.70–0.99], <em>P</em> = 0.042) and TKI resistance classification (acquired vs. primary: HR 2.28, 95 % CI [1.52–3.43], <em>P</em> = 0.001). Patients with primary TKI resistance showed improved outcomes with ICIs (median PFS 8.5 vs. 4.0 months; HR 0.46,<!--> <!-->95 % CI [0.29–0.76], <em>P</em> = 0.002), particularly in L858R-mutant subgroups. In contrast, acquired resistance cohorts—especially those with exon19del mutations—derived limited clinical benefit (HR 1.09, 95 % CI [0.84–1.42];<!--> <em>P</em> = 0.510). These findings suggest that resistance subtype and mutation profile may aid immunotherapy selection in EGFR-mutant NSCLC, requiring validation through prospective studies.</div></div><div><h3>Conclusions</h3><div>This multicenter analysis demonstrates that immunotherapy outcomes in EGFR-mutant NSCLC after TKI failure are influenced by both resistance subtypes (primary vs. acquired) and specific EGFR mutation profiles (L858R vs. exon19del). Patients with primary resistance and L858R mutations derive clinically meaningful benefit from ICIs, while those with acquired resistance, particularly exon19del variants, showed limited efficacy. These findings support further investigation of resistance-phenotype-guided therapeutic algorithms in prospective trials to optimize treatment sequencing strategies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"207 ","pages":"Article 108715"},"PeriodicalIF":4.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes and neuroendocrine features of transformed versus primary small-cell lung cancer","authors":"Lina Chen ,&nbsp;Xiu-Hao Zhang ,&nbsp;Zi-Ji Mao ,&nbsp;Dan Wang ,&nbsp;Chan-Yuan Zhang ,&nbsp;Hua-Jun Chen ,&nbsp;Yi-Long Wu ,&nbsp;Jin-Ji Yang","doi":"10.1016/j.lungcan.2025.108714","DOIUrl":"10.1016/j.lungcan.2025.108714","url":null,"abstract":"<div><h3>Introduction</h3><div>The clinical outcomes of transformed small-cell lung cancer (T-SCLC) was previously considered comparable with primary SCLC (P-SCLC). However, whether T-SCLCs and P-SCLCs differ in the era of immunotherapy remains unclear.</div></div><div><h3>Methods</h3><div>Clinical outcomes were retrospectively analyzed. Overall survival (OS) was estimated using the Kaplan–Meier method and Cox regression. Linear correlation and regression analyses were used to assess prognostic value of baseline neuron-specific enolase (NSE). Hierarchical clustering was used to group neuroendocrine (NE) markers of T-SCLC by immunohistochemical results.</div></div><div><h3>Results</h3><div>Between March 2018 and March 2023, 206 patients with T-SCLC (n = 42) and P-SCLC (n = 164) were enrolled in the study. The median OS (mOS) of T-SCLC cohort was significantly shorter than that of the P-SCLC cohort (11.7 vs. 12.9 months, <em>P</em> = 0.033). In the T-SCLC cohort, the mOS of chemoimmunotherapy significantly outlasted that of chemotherapy (15.4 vs. 8.5 months, <em>P</em> = 0.001). The optimal baseline NSE cutoff values differed between T-SCLC (19.7 ng/ml) and P-SCLC (74.8 ng/ml), and a high NSE level was associated with poorer mOS in both T-SCLC (10.0 vs. 16.5 months, <em>P</em> = 0.003) and P-SCLC (10.8 vs. 16.5 months, <em>P &lt;</em> 0.001). The cluster with stronger expression of NE markers in T-SCLC exhibited longer mOS (14.3 vs. 10.3 months, <em>P</em> = 0.030).</div></div><div><h3>Conclusion</h3><div>T-SCLC had a statistically poorer prognosis than P-SCLC, but the difference was modest. Chemoimmunotherapy might improve the outcomes of T-SCLC. Patients with T-SCLC who show stronger neuroendocrine features may have a poorer prognosis.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"207 ","pages":"Article 108714"},"PeriodicalIF":4.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T for Lung Cancers: Challenges and Innovations","authors":"Lucia Trudu ,&nbsp;Giulia Rovesti ,&nbsp;Giovanni Neri ,&nbsp;Giuseppe Pugliese ,&nbsp;Marco Silingardi ,&nbsp;Leonardo Brini ,&nbsp;Giulia Golinelli ,&nbsp;Maria Cristina Baschieri ,&nbsp;Eleonora Lallo ,&nbsp;Giorgia Guaitoli ,&nbsp;Federica Bertolini ,&nbsp;Cinzia Del Giovane ,&nbsp;Pier Luigi Filosso ,&nbsp;Massimo Dominici ,&nbsp;Chiara Chiavelli","doi":"10.1016/j.lungcan.2025.108711","DOIUrl":"10.1016/j.lungcan.2025.108711","url":null,"abstract":"<div><div>Lung cancer (LC) is the leading cause of cancer mortality worldwide. Despite current therapies, including surgery, radiotherapy, targeted therapies, and immunotherapy, most patients experience relapse. Immune checkpoint inhibitors (ICIs) have revolutionized LC treatment, but only a subset of patients benefit from them. Chimeric antigen receptor (CAR) T cell therapy emerges as an innovative and promising strategy in oncology. CAR T cells are genetically modified T lymphocytes that express a chimeric receptor specific for a tumor antigen. Very promising in hematology, CAR T has so far struggled to be transferred into the clinic for solid tumors, including LC. CAR T strategy against LC presents challenges in the selection of the optimal antigen to avoid off-target effects, for the known antigen heterogeneity and immunosuppressive environment of LC and the relatively short persistence of CAR T that may encounter disseminated diseases. Despite these limitations, here we describe growing preclinical and clinical studies that are exploring various LC antigens for CAR T within a variety of novel approaches and combinatorial strategies to overcome the barriers. Considering this emerging critical mass and despite the limits, we expect this endeavour to translate a fraction CAR T into clinical practice with efficacy against the still deadly LCs.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"207 ","pages":"Article 108711"},"PeriodicalIF":4.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pemetrexed plus platinum as second-line treatment for patients with pleural mesothelioma treated with nivolumab plus ipilimumab","authors":"Sawana Ono ,&nbsp;Hirokazu Taniguchi ,&nbsp;Koji Kuroda ,&nbsp;Teppei Hashimoto ,&nbsp;Asuka Okada ,&nbsp;Yasuhiro Goto ,&nbsp;Hidenori Kitai ,&nbsp;Yoichi Nakamura ,&nbsp;Shinsuke Ogusu ,&nbsp;Tetsunari Hase ,&nbsp;Takayo Ota ,&nbsp;Noriyuki Ebi ,&nbsp;Makoto Furugen ,&nbsp;Taishi Harada ,&nbsp;Yoshiaki Kinoshita ,&nbsp;Takaki Mizoguchi ,&nbsp;Katsumi Nakatomi ,&nbsp;Yoshifumi Soejima ,&nbsp;Takahiro Yamada ,&nbsp;Shinnosuke Takemoto ,&nbsp;Hiroshi Mukae","doi":"10.1016/j.lungcan.2025.108709","DOIUrl":"10.1016/j.lungcan.2025.108709","url":null,"abstract":"<div><div>There is limited evidence regarding the second-line treatment for patients with unresectable, advanced, or metastatic pleural mesothelioma receiving first-line nivolumab plus ipilimumab combination immunotherapy. Although chemotherapy with pemetrexed and a platinum-based agent is empirically administered as the second-line treatment in clinical practice, its effect in patients after nivolumab plus ipilimumab remains unclear. Therefore, this retrospective observational study aimed to elucidate the efficacy of pemetrexed plus platinum therapy as a second-line treatment for pleural mesothelioma after first-line nivolumab-ipilimumab immunotherapy. Forty-three patients with unresectable or advanced pleural mesothelioma were enrolled in this study. Median overall survival was 17.1 months (95 % confidence interval [CI]: 9.3- not estimable), and median progression-free survival was 5.7 months (95 % CI: 3.9–11.9). The one-year overall survival rate was 62.8 % (95 % CI: 45.0–76.3) and one-year progression-free survival rate was 26.2 % (95 % CI: 10.4–45.2). In patients with measurable lesions, the overall response rate was 30.3 % and disease control rate was 69.7 %. These results are similar to those of previous studies on pemetrexed-platinum for pleural mesothelioma in first-line settings, suggesting that pemetrexed-platinum therapy can be considered an appropriate choice for the second-line treatment of mesothelioma after immunotherapy.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"207 ","pages":"Article 108709"},"PeriodicalIF":4.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second-hand smoke and survival in former smokers with lung cancer: time to act.","authors":"Akbar Shoukat Ali, Muhammad Irfan","doi":"10.1016/j.lungcan.2025.108713","DOIUrl":"https://doi.org/10.1016/j.lungcan.2025.108713","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":" ","pages":"108713"},"PeriodicalIF":4.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dacomitinib in the treatment of EGFR-mutated non-small cell lung cancer with brain metastases: an open-label, multicenter, phase II study","authors":"Yongfeng Yu ,&nbsp;Yueyin Pan ,&nbsp;Jianya Zhou ,&nbsp;Shuya Mu ,&nbsp;Shun Lu","doi":"10.1016/j.lungcan.2025.108710","DOIUrl":"10.1016/j.lungcan.2025.108710","url":null,"abstract":"<div><h3>Objectives</h3><div>Dacomitinib’s efficacy in patients with severe brain metastases remains understudied. This study aimed to evaluate dacomitinib in treatment-naïve non-small-cell lung cancer (NSCLC) patients with EGFR mutations and multiple brain metastases.</div></div><div><h3>Methods</h3><div>This open-label, multicenter, Phase II study enrolled 15 treatment-naïve NSCLC patients with ≥3 brain metastases, including at least one lesion &gt;1 cm. Patients received dacomitinib 45 mg/day orally. Primary endpoints included progression-free survival (PFS), while secondary endpoints encompassed objective response rate (ORR), disease control rate (DCR), intracranial ORR (iORR), intracranial PFS (iPFS), and the incidence of treatment-emergent adverse events (TEAEs). Exploratory analyses were conducted to evaluate the influence of different types of EGFR mutations on the clinical outcomes. This study was registered in <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT04339829) and is closed to accrual.</div></div><div><h3>Results</h3><div>The median PFS was 16.8 months (95 % CI: 15.376, NE), with an overall ORR of 93.3 % (95 % CI: 68.052 %, 99.831 %) and DCR of 100 %. Intracranial efficacy was notable, with an iORR of 66.7 % (95 % CI: 38.380 %, 88.176 %) and median iPFS of 16.6 months (95 % CI: 3.614, NE). Among patients evaluated for intracranial response, the iORR reached as high as 90.9 %. Exploratory analyses revealed no significant differences in PFS, iPFS, or disease progression based on exon 19 deletions or L858R mutations. Six patients (40 %) experienced ≥grade 3 TEAEs which were manageable.</div></div><div><h3>Conclusion</h3><div>Dacomitinib demonstrated robust systemic and intracranial efficacy in patients with NSCLC harboring EGFR mutations and severe brain metastases, with acceptable adverse events, thereby supporting its use as a first-line treatment.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"207 ","pages":"Article 108710"},"PeriodicalIF":4.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A treatment-impact model of alectinib for the prediction of recurrence and associated costs in treating resectable ALK+ non-small cell lung cancer","authors":"Amy L. Cummings ,&nbsp;Jesse Sussell ,&nbsp;Katherine L. Rosettie ,&nbsp;Fadoua El Moustaid ,&nbsp;Sarika Ogale ,&nbsp;Celina Ngiam ,&nbsp;Nick Jovanoski ,&nbsp;Melina Arnold ,&nbsp;Jay M. Lee","doi":"10.1016/j.lungcan.2025.108701","DOIUrl":"10.1016/j.lungcan.2025.108701","url":null,"abstract":"<div><h3>Objectives</h3><div>Based on the Phase III ALINA trial, alectinib gained US approval as the first anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor for adjuvant treatment of resectable ALK + non-small cell lung cancer (NSCLC). We used a treatment impact model to estimate associated population-level clinical benefits and cost savings of alectinib vs chemotherapy.</div></div><div><h3>Materials and Methods</h3><div>Treatment-associated costs for alectinib vs chemotherapy were estimated for five annual cohorts of US patients with stage IB-IIIA ALK+ NSCLC between 2024 and 2028; each cohort was followed for 10 years. Data sources included ALINA. Two treatment scenarios were modelled, with all patients receiving adjuvant treatment with (1) alectinib and (2) chemotherapy. For each scenario, the model simulated the number of patients who received adjuvant treatment and experienced metastatic or non-metastatic recurrence or death and treatment-associated and downstream recurrence costs. Key assumptions were varied in sensitivity analyses. The impact of joint parameter uncertainty was evaluated using probabilistic sensitivity analysis.</div></div><div><h3>Results</h3><div>In 2024–2028, an estimated 3,130 patients with resectable ALK+ NSCLC would be eligible for adjuvant alectinib treatment. Relative to chemotherapy, alectinib was estimated to prevent 1,531 recurrences and deaths, including 1,059 recurrences to metastatic NSCLC, thus avoiding of $1.31 billion (USD) in costs associated with recurrences and death. Considering upfront adjuvant treatment costs, alectinib was estimated to save $347 million vs chemotherapy.</div></div><div><h3>Conclusions</h3><div>Adjuvant alectinib treatment improved population-level clinical outcomes and was predicted to generate cost savings in the US. Predicted alectinib benefits were maximized when all indicated patients were tested for the ALK biomarker.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"207 ","pages":"Article 108701"},"PeriodicalIF":4.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The survival analysis of stage III and IV inoperable lung large cell neuroendocrine carcinoma and the role of LIPI in immunological stratification","authors":"Ru Li ,&nbsp;Wenxia Xie ,&nbsp;Rui Chen ,&nbsp;Jianhui Wu ,&nbsp;Liqiang Wang ,&nbsp;Yuhan Sun ,&nbsp;Xinqing Lin ,&nbsp;Xiaohong Xie ,&nbsp;Zhanhong Xie ,&nbsp;Laiyu Liu ,&nbsp;Ming Liu ,&nbsp;Chengzhi Zhou","doi":"10.1016/j.lungcan.2025.108698","DOIUrl":"10.1016/j.lungcan.2025.108698","url":null,"abstract":"<div><h3>Background</h3><div>Large cell neuroendocrine carcinoma (LCNEC) represents a rare and unique type of lung tumor with an unfavorable prognosis. It is essential to summarize the treatment modalities and prognosis for inoperable stage III and IV LCNEC, explore the role of frontline immunotherapy, and examine the stratification role of the Lung Immune Prognostic Index (LIPI) and its relationship with the tumor microenvironment (TME).</div></div><div><h3>Methods</h3><div>This study retrospectively analyzed 160 patients with inoperable lung LCNEC (L-LCNEC) admitted to three hospitals from December 2012 to November 2023. We evaluated the effects of different systemic treatment modalities on prognosis and explored independent prognostic factors, establishing models incorporating blood indicators. Furthermore, the study aimed to assess the association of the LIPI with overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in patients receiving immune checkpoint inhibitors (ICIs).</div></div><div><h3>Results</h3><div>Patients receiving frontline immunotherapy had significantly higher ORR (52.0 % vs. 24.7 %, p &lt; 0.001), PFS (6.33 vs. 2.93 months, p = 0.033) and OS (21.3 vs. 12.9 months, p = 0.034). Independent protective factors for OS included frontline immunotherapy (p = 0.008) and CK positive expression (p = 0.033), while poor LIPI (p = 0.023), ≥3 metastatic sites (p = 0.005), positive CgA expression (p = 0.016), and DD-2 ≥ 5.0 (p &lt; 0.001) were identified as independent risk factors. A prognostic model based on these factors had an AUC of 0.749. Significant differences in median PFS (mPFS) and median OS (mOS) were observed among the good, intermediate, and poor LIPI groups (p &lt; 0.05). Multiple immunofluorescence staining revealed that the good LIPI group exhibited greater infiltration of immune cells marked by CD3 antibody.</div></div><div><h3>Conclusion</h3><div>This study highlights the benefit of frontline immunotherapy and the importance of LIPI in prognosis stratification, especially in identifying patients with limited treatment benefit.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"208 ","pages":"Article 108698"},"PeriodicalIF":4.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential: tissue mutation abundance as a predictor for third-generation EGFR-TKI efficacy in NSCLC","authors":"Ruiqi Wang ,&nbsp;Hongfei Wei ,&nbsp;Chunjing Qu ,&nbsp;Yuansong Bai ,&nbsp;Wenlong Zhang","doi":"10.1016/j.lungcan.2025.108699","DOIUrl":"10.1016/j.lungcan.2025.108699","url":null,"abstract":"<div><h3>Background</h3><div>Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are recommended as first-line treatment for patients with unresectable non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations, but few studies have explored the role of tissue mutation abundance in predicting their efficacy. To optimize targeted treatments, this study compares the efficacy of first-line third-generation EGFR-TKIs in unresectable NSCLC patients with EGFR-sensitive mutations, focusing on tissue mutation abundance.</div></div><div><h3>Methods</h3><div>The study retrospectively analyzed clinical data from 697 patients, ultimately including 159 after screening. Differences in treatment response and median progression-free survival (mPFS) between these groups were examined, and risk factors for mPFS were identified through univariate and multivariate analyses. The disease progression patterns of the two groups were also compared.</div></div><div><h3>Results</h3><div>There was no notable difference in complete and partial response rates between the groups. However, the high-abundance group had significantly higher objective response rate (88 % <em>vs.</em> 66.7 %, <em>p</em> = 0.032) and disease control rates (97.2 % <em>vs.</em> 80.4 %, <em>p</em> &lt; 0.001). The mPFS was also longer in the high-abundance group (22 months <em>vs.</em> 17 months, <em>p</em> = 0.024). In the high-abundance group, factors like mutation site, metastasis types and co-existing PI3KCA mutations affected mPFS in univariate analysis, but not in multivariate analysis. In the low-abundance group, ECOG PS and tumor site influenced mPFS. Both groups showed similar patterns of disease progression, including in situ tumor, visceral, bone, and brain metastasis, without statistical significance.</div></div><div><h3>Conclusions</h3><div>In unresectable NSCLC with EGFR-sensitive mutations, tissue mutation abundance predicts the efficacy of third-generation TKIs. Patients with high mutation abundance consistently experience longer mPFS. Those with low abundance and peripheral lung cancer also have relatively long mPFS, but other low abundance cases show quick resistance and progression. Further research is needed to create more precise, personalized treatments for these patients.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"207 ","pages":"Article 108699"},"PeriodicalIF":4.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}