Translational lung cancer research最新文献

{"title":"Radiotherapy as salvage therapy and an adjunct to immunotherapy: exploring local and abscopal mechanisms to overcome immunotherapy resistance: a narrative review.","authors":"Yunxin Yang, Tong Liu, Song Mi, Xin Liu, Salma K Jabbour, Ning Liang, Guodong Deng, Pingping Hu, Jiandong Zhang","doi":"10.21037/tlcr-2025-57","DOIUrl":"10.21037/tlcr-2025-57","url":null,"abstract":"<p><strong>Background and objective: </strong>Immune checkpoint inhibitors (ICIs) have ushered in a new era of therapies and play a significant role in the clinical treatment of a variety of tumors. However, immune resistance has increasingly created a bottleneck in treatment, making the question of how to overcome drug resistance an urgent issue to address. In this article, the mechanism of drug resistance is briefly described with a focus on how radiotherapy (RT) acts on the immune system to reverse immunotherapy failure. Combinations of existing treatment modalities need to be optimized to overcome resistance problems. Research has shown that some RT modalities reverse immune resistance or enhance efficacy when used in combination, which shows some value for immune resistance and is worthy of in-depth research.</p><p><strong>Methods: </strong>In this review, we searched the literature published from 2000 to 2023 surrounding immunotherapy, RT and cancer.</p><p><strong>Key content and findings: </strong>Based on the immune effects and immunosuppressive effects induced by RT, this review examined the preclinical rationales of RT and its clinical results. The findings indicate that RT might provide a novel regimen for patients with locally advanced tumors, especially oligometastatic tumors.</p><p><strong>Conclusions: </strong>Salvage therapy with RT after immunotherapy resistance is the focus of current research. Other strategies, such as multidrug combination therapies, have made preliminary progress in preclinical experiments. Further research on the roles of different RT doses, fractionation regimens, and other treatment sequences in salvage therapy need to be conducted in the future. The optimal site and timing of low-dose radiotherapy are also undetermined, and prospective studies are need to determine the best regimen for optimizing patient treatment.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"591-606"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671119","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":"Study of the radiologic and pathologic correlations for subsolid lung adenocarcinoma with the application of whole-mount sections (ECTOP1011).","authors":"Ting Ye, Xuxia Shen, Shengping Wang, Haoxuan Wu, Yue Wang, Hong Hu, Yang Zhang, Qingyuan Huang, Zezhou Wang, Yajia Gu, Yuan Li, Haiquan Chen","doi":"10.21037/tlcr-2024-1063","DOIUrl":"10.21037/tlcr-2024-1063","url":null,"abstract":"<p><strong>Background: </strong>The radiologic and pathologic correlations of subsolid lung cancers are unclear. No study has used the whole-mount sections to analyze the correlations. This study aims to clarify the radiologic and pathologic correlations through the use of the whole-mount sections analysis.</p><p><strong>Methods: </strong>Patients with subsolid lung adenocarcinomas receiving segmentectomy or lobectomy were included. The whole-mount sections were made. The same radiologic and pathologic sections were identified. Radiologic and pathologic tumor and solid/invasive sizes were compared. Histologic features in the solid component and ground-glass opacity (GGO) regions were evaluated.</p><p><strong>Results: </strong>There were 102 patients with 20 pure GGO and 82 part-solid tumors analyzed. There was one adenocarcinoma <i>in situ</i>, 32 minimal invasive adenocarcinomas, and 69 invasive adenocarcinomas. For all patients or patients with the matched sections, radiologic tumor diameter was larger than pathologic one (P<0.001; P=0.009), while radiologic solid component diameter was smaller than that of pathologic invasive diameter (P=0.01; P<0.001). The clinical T stage was pathologically upstaged in nearly 50% of patients. For pure GGO tumors, prevalence of lepidic, acinar, and papillary subtypes was 100.0%, 84.2%, and 47.4%, with no micropapillary or solid subtype. For part-solid tumors, in the GGO region, prevalence of lepidic, acinar, papillary, and micropapillary subtypes was 100.0%, 83.3%, 57.1%, and 11.9%, no solid subtype existed. In the solid region, prevalence of lepidic, acinar, papillary, micropapillary, and solid subtypes was 19.0%, 95.2%, 59.5%, 26.2%, and 2.3%.</p><p><strong>Conclusions: </strong>For subsolid lung cancers, the pathologic invasive size was radiologically underestimated. There were acinar/papillary, but no micropapillary subtype in pure GGO tumors. In part-solid tumors, there were micropapillary subtypes in GGO region and micropapillary/solid subtypes in solid region.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"341-352"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670832","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":"Predictive value of perioperative carcinoembryonic antigen changes for recurrence in non-small cell lung cancer.","authors":"Hua Sun, Sikai Wu, Zhongxiao Chen, Hao Liu, William C Cho, Pasan Witharana, Minhua Ye, Dehua Ma, Chunguo Wang, Chengchu Zhu, Jianfei Shen","doi":"10.21037/tlcr-24-776","DOIUrl":"10.21037/tlcr-24-776","url":null,"abstract":"<p><strong>Background: </strong>Despite surgical resection, the prognosis for patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. The objective of this study was to investigate the impact of serum carcinoembryonic antigen (CEA) levels on recurrence in patients with NSCLC before and after surgical resection. In addition, for patients with invasive lung adenocarcinoma (IAC), which constitutes the majority of cases, we further explored the effect of pathological subtype on recurrence.</p><p><strong>Methods: </strong>A total of 349 patients were included in the study. The correlation between clinicopathological factors and post-surgery survival outcomes was analyzed. Kaplan-Meier curves were constructed based on the pertinent data and analyzed using the Cox regression model. Recurrence risk curves were plotted according to the time to recurrence for each CEA subgroup and pathological subtype to explore the change in recurrent rate over time in each group.</p><p><strong>Results: </strong>A total of 9 (81.82%) patients in the low preoperative CEA but higher than normal postoperative CEA levels group experienced recurrence, with a median recurrence-free survival (RFS) of only 24 months and a median overall survival (OS) of 57 months. These outcomes demonstrated poorer RFS and OS than those observed in the other three groups. Multivariate analysis of RFS revealed postoperative CEA level (P<0.001), histological type (P=0.01), tumour size (P=0.048), tumor-node-metastasis (TNM) stage (P<0.001) and pN stage (P=0.04) as independent poor prognostic factors. postoperative CEA level (P=0.003), histological type (P=0.02), tumor size (P=0.03), TNM stage (P=0.004) and pN stage (P=0.049) were independent poor prognostic factors for OS. Among the pathological subtypes, patients with Grade 3 (high-grade patterns ≥20%) exhibited a higher risk of recurrence after surgery.</p><p><strong>Conclusions: </strong>Elevated CEA levels in the postoperative period, as well as pathological subtypes of Grade 3, have been identified as risk factors for early recurrence in NSCLC patients after surgery.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"398-407"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671106","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":"Light on the horizon for HER2 overexpressing non-small cell lung cancer?","authors":"Kira-Lee Koster, Martin Früh","doi":"10.21037/tlcr-24-859","DOIUrl":"10.21037/tlcr-24-859","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"305-309"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671020","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":"Sleeve lobectomy versus lobectomy after neoadjuvant chemo-immunotherapy for non-small cell lung cancer invading the lobar bronchial orifice: a multicenter retrospective cohort study.","authors":"Tianyue Ma, Jun Yi, Yong Ge, Haitang Yang, Jiayi Wang, Shuyuan Li, Ran Ma, Guodong Zhang, Hao Peng, Pingping Song, Feng Yao, Hao Zhang","doi":"10.21037/tlcr-24-925","DOIUrl":"10.21037/tlcr-24-925","url":null,"abstract":"<p><strong>Background: </strong>For non-small cell lung cancer (NSCLC) invading lobar bronchial orifice, sleeve lobectomy is the preferred surgical option. Neoadjuvant chemo-immunotherapy may allow R0 resection with lobectomy. This study aims to compare the long-term outcome of sleeve lobectomy and lobectomy after neoadjuvant chemo-immunotherapy.</p><p><strong>Methods: </strong>We retrospectively screened patients undergoing neoadjuvant chemo-immunotherapy followed by lobectomy or sleeve lobectomy for NSCLC invading lobar bronchial orifice from March 2019 and April 2022. Event-free survival (EFS) was compared between sleeve lobectomy and lobectomy groups in the original cohort and the inverse probability of treatment weighting (IPTW) adjusted cohort. Cox regression was conducted for the potential association between surgical type and EFS.</p><p><strong>Results: </strong>We initially enrolled 248 patients. According to the inclusion criteria, the final analysis included 68 (27.4%) patients: 38 undergoing lobectomy and 30 undergoing sleeve lobectomy. The 2-year EFS was 83.3% versus 60.5% in sleeve and lobotomy groups, respectively [hazard ratio (HR) =0.46, 95% confidence interval (CI): 0.210-1.005; P=0.057]. In Cox regression analysis, improved EFS was associated with pathological complete response (pCR) (HR =0.31, 95% CI: 0.11-0.90; P=0.03) but not surgical types (HR =0.54, 95% CI: 0.22-1.5; P=0.20). In the subgroup analysis including pCR patients (n=31), median EFS was not reached (NR) in either group (P=0.8) before and after IPTW. In the non-pCR subgroup (n=37), median EFS was 21 months (95% CI: 13-NR) in lobectomy group versus not achieved (95% CI: 25-NR) in sleeve lobectomy group (P=0.04) after IPTW.</p><p><strong>Conclusions: </strong>Lobectomy could be feasible for pCR patients and there is survival advantage with sleeve lobectomy in patients failing to achieve pCR after neoadjuvant chemo-immunotherapy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"408-421"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670830","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":"Sunvozertinib: shining light on lung cancer's exon 20 fight.","authors":"Tetsuya Mitsudomi","doi":"10.21037/tlcr-24-907","DOIUrl":"10.21037/tlcr-24-907","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"334-340"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670833","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":"Clinical application of three-dimensional reconstruction in anatomical analysis of the right anterior, lateral, and posterior basal segments (RS8, RS9, and RS10) for RS9 segmentectomy.","authors":"Jiafu Zhu, Sui Chen, Yukang Lin, Jiangshan Huang, Marcus Taylor, Junji Ichinose, Yeon Wook Kim, Zihao Zheng, Jinyang Shi, Litao Yang, Jiangbo Lin","doi":"10.21037/tlcr-2024-1231","DOIUrl":"10.21037/tlcr-2024-1231","url":null,"abstract":"<p><strong>Background: </strong>Anatomical RS9 segmentectomy is challenging due the intricate intersegmental planes (ISPs) and varied anatomical structures involved, with few studies having robustly assessed the three-dimensional (3D) reconstruction techniques for the anatomy and surgical procedures of the RS9 segment. This study aimed to analyze the application of 3D reconstruction for the vascular and bronchial branching patterns of the right anterior, lateral, and posterior basal segments (RS8, RS9, and RS10, respectively) for anatomical RS9 segmentectomy.</p><p><strong>Methods: </strong>From May 2020 to May 2022, 3D reconstructions of 354 patients were retrospectively analyzed in terms of vascular and bronchial branching patterns using Mimics 21.0 (Materialise). Based on the preoperative and intraoperative 3D reconstruction data, anatomical RS9 segmentectomy was performed in 27 patients, and the surgical outcomes were retrospectively analyzed.</p><p><strong>Results: </strong>The branching patterns of the right basal bronchi (B8, B9, and B10) were divided into the B8 and B9+10 type (74.6%); the B8+9 and B10 type (15.3%); and the B8, B9, and B10 type (10.2%). The branching patterns of the right basal arteries (A8, A9, and A10) were classified into a simple bifurcated type [the A8 and A9+10 type (62.4%) and the A8+9 and A10 type (13.0%)], split bifurcated type [the A8 and A8+9+10 type (18.4%) and the A8+9 and A9+10 type (3.7%)], and trifurcated type [the A8, A9, and A10 type (2.5%)]. The branching patterns of the right basal veins (V8, V9, and V10) were complex and were classified into simple bifurcated, split bifurcated, and trifurcated types and further divided into 10 subtypes. Of these types, the V8+9 and V10 type, the V8+9+10 and V10 type, and the V8+9 and V9+10 type were the most common, accounting for 29.4%, 25.4%, and 21.5% of the cases, respectively. Anatomical RS9 segmentectomy was successfully completed without conversion to thoracotomy in all 27 patients.</p><p><strong>Conclusions: </strong>3D reconstruction is a practical tool for analyzing the bronchovascular branching patterns of RS8, RS9, and RS10. The application of 3D reconstruction is safe and feasible in anatomical RS9 segmentectomy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"513-525"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670851","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":"Comparative outcomes of first-line PD-1/PD-L1 inhibitors plus chemotherapy for advanced squamous non-small cell lung cancer: a systematic review and network meta-analysis of randomized clinical trials.","authors":"Zhefeng Liu, Zhikuan Wang, Jun Zhu, Haitao Tao, Ziwei Huang, Lu Han, Akshay J Patel, Yi Hu","doi":"10.21037/tlcr-2025-83","DOIUrl":"10.21037/tlcr-2025-83","url":null,"abstract":"<p><strong>Background: </strong>Head-to-head comparisons between the available first-line regimens with programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors and chemotherapy for advanced squamous non-small cell lung cancer (NSCLC) are lacking. Therefore, we conducted a systematic review and network meta-analysis to identify the optimal first-line regimen with PD-1/PD-L1 inhibitors plus chemotherapy for advanced squamous NSCLC.</p><p><strong>Methods: </strong>A systematic review and network meta-analysis of randomized clinical trials (RCTs) were performed. PubMed, Embase, Web of Science, and the ClinicalTrials.gov databases and major annual conferences were searched. RCTs that compared PD-1/PD-L1 inhibitors plus chemotherapy with chemotherapy alone in patients with advanced squamous NSCLC were eligible for inclusion. Risk of bias was assessed using the Cochrane Risk of Bias Tool (version 2.0), and a funnel plot was used to assess the publication bias.</p><p><strong>Results: </strong>A total of nine RCTs comprising 3,210 patients were included. When combined with chemotherapy, PD-1 inhibitors were superior to PD-L1 inhibitors in terms of overall survival (OS) [PD-1: hazard ratio (HR) 0.70, 95% credible interval (CrI): 0.62 to 0.79; PD-L1: HR 0.82, 95% CrI: 0.71 to 0.94] and progression-free survival (PFS) (PD-1: HR 0.50, 95% CrI: 0.45 to 0.55; PD-L1: HR 0.63, 95% CrI: 0.55 to 0.72). Moreover, the PD-1 inhibitor camrelizumab was the most effective agent in combined therapy for prolonging OS (HR 0.56, 95% CrI: 0.44 to 0.71) and PFS (HR 0.32, 95% CrI: 0.25 to 0.42), followed by the PD-L1 inhibitor sugemalimab (OS: HR 0.61, 95% CrI: 0.43 to 0.86; PFS: HR 0.37, 95% CrI: 0.26 to 0.52). Moreover, the addition of camrelizumab or tislelizumab to chemotherapy was associated with the improved objective response rate (ORR) and a longer duration of response (DoR). Regarding safety, pembrolizumab and camrelizumab were associated with the lowest risk of developing grade 3-5 treatment-related adverse events (TRAEs). Most of the trials were at low risk for bias, and no obvious publication bias was observed in the outcomes.</p><p><strong>Conclusions: </strong>When combined with first-line chemotherapy, camrelizumab has the potential to be a preferred option in patients with advanced squamous NSCLC. This finding might serve as a guideline to aid in the selection of first-line immunotherapy plus chemotherapy strategies for advanced squamous NSCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"563-574"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670869","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":"Real-world comparison of neoadjuvant pembrolizumab plus chemotherapy versus tislelizumab plus chemotherapy in patients with resectable non-small cell lung cancer: a retrospective cohort study of treatment outcomes.","authors":"Yan Hu, Siying Ren, Juan Feng, Chao Zeng, Lulu Yang, Jinyou Liu, Fang Wu, Wenliang Liu","doi":"10.21037/tlcr-24-721","DOIUrl":"10.21037/tlcr-24-721","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Pembrolizumab and tislelizumab have shown substantial clinical benefits in perioperative treatment of resectable non-small cell lung cancer (NSCLC), yet no direct head-to-head trial has established which is optimal. This study, for the first time, aimed to directly compare the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy versus tislelizumab plus chemotherapy in resectable NSCLC using real-world data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data of patients with resectable NSCLC treated with neoadjuvant pembrolizumab plus chemotherapy or tislelizumab plus chemotherapy followed by radical resection between December 2017 and August 2023 at the Second Xiangya Hospital of Central South University were retrospectively analyzed. Patients aged 18 years and above, diagnosed with biopsy-proven and treatment-naïve clinical stage II-IIIb NSCLC were included in the study. Patients with autoimmune disease, pulmonary interstitial disease, acute infection, or systemic immunosuppression were excluded. Data that may affect treatment efficacy were collected, including age, sex, body mass index (BMI), smoking history, comorbidities, pulmonary function, pathological type, clinical stage, programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS), dosage of neoadjuvant therapy, duration from final therapy to surgery and chemotherapy regimens, and compared between the two groups. The follow-up was performed through outpatient visits or telephone calls. The last follow-up was set in June 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 126 patients were included and divided into the pembrolizumab (n=62) and tislelizumab (n=64) groups with a median follow-up time of 26.3 months. The mean age at diagnosis was 59.76 years (standard deviation, 7.05 years) and 103 patients (81.75%) were current or former smoker. Squamous cell carcinoma (SCC) (102, 80.95%) was the most common histological type, followed by adenocarcinoma (18, 14.29%), large cell neuroendocrine carcinoma (2, 1.59%) and sarcomatoid carcinoma (2, 1.59%). Although there was a lower proportion of SCC (72.58% &lt;i&gt;vs.&lt;/i&gt; 89.06%, P=0.02) and a lower use of paclitaxel (75.81% &lt;i&gt;vs.&lt;/i&gt; 96.88%, P=0.004) in the pembrolizumab group in the overall cohort, the baseline characteristics between two groups were balanced in the SCC cohort. No significant differences in objective response rate, percentage of primary tumors with no viable tumor cells, pathologic and lymph node downstaging, pathological complete response and major pathological response existed between the two groups in both cohorts. Additionally, disease-free survival and overall survival were similar between the two groups in both cohorts. No significant differences in the postoperative complications and grade 3/4 toxicity profiles existed in both cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This real-world evidence study supports the non-inferiority of neoadjuvant pembrolizumab plus chemotherapy versus tis","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"467-479"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670142","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":"Whole-section digital analysis of immune profiles in surgically resected small cell lung carcinoma and their associations with molecular subtypes.","authors":"Yanli Zhu, Jianghua Wu, Haiyue Wang, Kaiwen Chi, Xinting Diao, Minglei Zhuo, Dongmei Lin","doi":"10.21037/tlcr-24-924","DOIUrl":"10.21037/tlcr-24-924","url":null,"abstract":"<p><strong>Background: </strong>The molecular subtype-specific features of the tumor immune microenvironment (TIME) in small cell lung carcinoma (SCLC) remain poorly understood. We aimed to analyze the immune profiles in surgically resected SCLC and their associations with molecular subtypes.</p><p><strong>Methods: </strong>Tumor samples from 83 treatment-naive SCLC patients who underwent surgical resection were analyzed. The protein expression of subtype-defining markers (ASCL1, NEUROD1, POU2F3, and YAP1) and nine immune-related markers were assessed using whole-section immunohistochemistry. Digital image analysis was employed for precise quantification of immune cell infiltrates and distributions. The findings were subsequently correlated with clinicopathological parameters and patient prognoses.</p><p><strong>Results: </strong>Unsupervised hierarchical clustering categorized the tumors into four molecular subtypes: achaete-scute homologue 1-dominant (ASCL1; SCLC-A, 71.1%, n=59), neuronal differentiation factor 1-dominant (NEUROD1; SCLC-N, 12.1%, n=10), POU class 2 homeobox 3-dominant (POU2F3; SCLC-P, 10.8%, n=9), and quadruple-negative (SCLC-QN, 6.0%, n=5). Expression of major histocompatibility complex class I (MHC I) and class II (MHC II; P=0.02, P=0.02), tumor programmed death-ligand 1 (PD-L1; P=0.006), and an inflamed phenotype characterized by CD8⁺/CD3⁺ T cells (P=0.001, P=0.003) were more prominent in SCLC-P tumors compared to other subtypes. Additionally, SCLC-P tumors demonstrated the highest levels of MHC II (P=0.04) and PD-L1 expression on both tumor and stromal cells (P=0.003, P=0.01). The tumor proportion score of PD-L1 positively correlated with tumor expression levels of POU2F3 (rho=0.297, P=0.006) and MHC I (rho=0.239, P=0.03), as well as the combined positive score of PD-L1 (rho=0.222, P=0.04; rho=0.433, P<0.001). Intra-tumoral tertiary lymphoid structures (intra-TLS) and peri-tumoral TLS (peri-TLS) were observed in 60.2% (n=50) and 96.4% (n=80) of patients, respectively. High intra-TLS density was more frequently associated with SCLC-P tumors (P=0.02). Notably, low peri-TLS density and stromal PD-L1 expression were linked to improved overall survival (OS) and progression-free survival (PFS), respectively.</p><p><strong>Conclusions: </strong>This study highlights the heterogeneity of the TIME across molecular subtypes of SCLC. The SCLC-P subtype and MHC I expression may serve as predictive biomarkers for immunotherapy response, while peri-TLS density and stromal PD-L1 expression might serve as prognostic indicators in resected SCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"449-466"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670840","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}