Introduction: Studies have shown the antitumor efficacy of immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and brain metastases (BM). However, it is unclear whether the efficacy of ICI is similar between patients with and without BM. It is yet unclear whether the efficacy of ICI in patients with BM increases with higher levels of programmed cell death-ligand 1 (PD-L1) expression, as observed in patients without BM.
Methods: We compared the outcomes of ICI treatment between patients with and without BM using a cohort containing 1741 prospectively enrolled patients with lung cancer. We investigated whether there were differences in the outcomes of ICI based on PD-L1 expression levels between these patients.
Results: We enrolled 240 patients with NSCLC with or without BM who were treated with ICI or both chemotherapy and ICI. There were no significant differences in overall survival (OS) between all patients with or without BM (p = 0.489). However, OS was significantly shorter in patients with BM than in those without in the PD-L1 ≥ 50% group (16.5 M vs. 30.6 M, p = 0.003) but not in the PD-L1 ≥ 1% or negative group. BM was an independent poor prognostic factor for OS (hazard ratio: [95% confidence interval], 2.045; [1.058-3.953], p = 0.033) in the PD-L1 ≥ 50% group.
Conclusion: Our study indicated that the outcomes of patients with or without BM treated with ICI were not significantly different. The efficacy of ICI in patients with PD-L1 expression ≥50% would be lower in patients with BM than in those without.
{"title":"Efficacy of immune checkpoint inhibitors according to programmed cell death-ligand 1 expression in patients with non-small cell lung cancer and brain metastasis: A real-world prospective observational study.","authors":"Takeshi Masuda, Yukari Tsubata, Kojirou Hata, Mika Horie, Katsuyuki Kiura, Nobuhiro Kanaji, Takuya Inoue, Masahiro Kodani, Masaaki Yanai, Kakuhiro Yamaguchi, Naoko Matsumoto, Masahiro Yamasaki, Nobuhisa Ishikawa, Ken Masuda, Nagio Takigawa, Shoichi Kuyama, Tetsuya Kubota, Kazuya Nishii, Katsuyuki Hotta, Noboru Hattori","doi":"10.1111/1759-7714.15469","DOIUrl":"https://doi.org/10.1111/1759-7714.15469","url":null,"abstract":"<p><strong>Introduction: </strong>Studies have shown the antitumor efficacy of immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and brain metastases (BM). However, it is unclear whether the efficacy of ICI is similar between patients with and without BM. It is yet unclear whether the efficacy of ICI in patients with BM increases with higher levels of programmed cell death-ligand 1 (PD-L1) expression, as observed in patients without BM.</p><p><strong>Methods: </strong>We compared the outcomes of ICI treatment between patients with and without BM using a cohort containing 1741 prospectively enrolled patients with lung cancer. We investigated whether there were differences in the outcomes of ICI based on PD-L1 expression levels between these patients.</p><p><strong>Results: </strong>We enrolled 240 patients with NSCLC with or without BM who were treated with ICI or both chemotherapy and ICI. There were no significant differences in overall survival (OS) between all patients with or without BM (p = 0.489). However, OS was significantly shorter in patients with BM than in those without in the PD-L1 ≥ 50% group (16.5 M vs. 30.6 M, p = 0.003) but not in the PD-L1 ≥ 1% or negative group. BM was an independent poor prognostic factor for OS (hazard ratio: [95% confidence interval], 2.045; [1.058-3.953], p = 0.033) in the PD-L1 ≥ 50% group.</p><p><strong>Conclusion: </strong>Our study indicated that the outcomes of patients with or without BM treated with ICI were not significantly different. The efficacy of ICI in patients with PD-L1 expression ≥50% would be lower in patients with BM than in those without.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-09-15DOI: 10.1111/1759-7714.15449
Bin Jia, Chen Chen, Ting Gong, Zhenfa Zhang, Bingsheng Sun
Background: Thymoma is a primary tumor of the thymus, commonly located in the anterior mediastinum. Most thymomas are benign or low-grade malignant, but they can invade surrounding organs or metastasize. The primary treatment for thymoma is surgical resection. Traditional methods involve open thoracotomy, but it is traumatic, with slow recovery and many complications. In recent years, with the development of thoracoscopic techniques, thoracoscopic total thymectomy has gradually become the preferred method for small size thymomas due to its minimally invasive, safe, and effective.
Methods: This paper introduces a thoracoscopic extend thymectomy technique, the subxiphoid video-assisted thoracoscopic extend thymectomy with sternal suspension. This method involves placing hooks at the upper and lower ends of the sternum to suspend the sternum upward, increasing the thoracic cavity space and facilitating thoracoscopic operations. This research reviews the clinical data of 59 patients with early-stage thymomas treated with this technique at our center since 2020 and analyzes the perioperative therapeutic efficacy and safety. It also compares the outcomes with those of 17 patients who underwent thoracoscopic approaches.
Results: The results show that subxiphoid video-assisted thoracoscopic total thymectomy with sternal suspension is an innovative and effective surgical method, achieving the same tumor eradication as other thoracic surgeries. The flexible switching of observation ports provides a more comprehensive surgical field, reduces surgical trauma and complications, and improves the surgical outcomes and quality of life for patients.
{"title":"Subxiphoid video-assisted thoracoscopic extend thymectomy with sternal suspension for thymoma.","authors":"Bin Jia, Chen Chen, Ting Gong, Zhenfa Zhang, Bingsheng Sun","doi":"10.1111/1759-7714.15449","DOIUrl":"10.1111/1759-7714.15449","url":null,"abstract":"<p><strong>Background: </strong>Thymoma is a primary tumor of the thymus, commonly located in the anterior mediastinum. Most thymomas are benign or low-grade malignant, but they can invade surrounding organs or metastasize. The primary treatment for thymoma is surgical resection. Traditional methods involve open thoracotomy, but it is traumatic, with slow recovery and many complications. In recent years, with the development of thoracoscopic techniques, thoracoscopic total thymectomy has gradually become the preferred method for small size thymomas due to its minimally invasive, safe, and effective.</p><p><strong>Methods: </strong>This paper introduces a thoracoscopic extend thymectomy technique, the subxiphoid video-assisted thoracoscopic extend thymectomy with sternal suspension. This method involves placing hooks at the upper and lower ends of the sternum to suspend the sternum upward, increasing the thoracic cavity space and facilitating thoracoscopic operations. This research reviews the clinical data of 59 patients with early-stage thymomas treated with this technique at our center since 2020 and analyzes the perioperative therapeutic efficacy and safety. It also compares the outcomes with those of 17 patients who underwent thoracoscopic approaches.</p><p><strong>Results: </strong>The results show that subxiphoid video-assisted thoracoscopic total thymectomy with sternal suspension is an innovative and effective surgical method, achieving the same tumor eradication as other thoracic surgeries. The flexible switching of observation ports provides a more comprehensive surgical field, reduces surgical trauma and complications, and improves the surgical outcomes and quality of life for patients.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"2185-2192"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition and is expressed at high levels. Furthermore, 5%-8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers. However, the clinical relevance of AMHR2 expression and its role in lung cancer is not fully clarified.
Methods: Immunostaining was performed on 79 surgical specimens of NSCLC. The Cancer Genome Atlas RNA-seq data for lung adenocarcinoma were analyzed, and gene ontology and gene set enrichment analyses were performed. In cellular experiments, AMHR2-overexpressing NSCLC cell lines were established, and the role of the AMH-AMHR2 pathway in cell proliferation with recombinant human AMH protein treatment was examined.
Results: A total of 13 cases (16.5%) were positive for immunostaining in lung adenocarcinoma tissues; no positive signals were detected in lung squamous carcinoma tissues. Gene expression variation analysis using The Cancer Genome Atlas data showed that the expression of genes related to the cell cycle was downregulated in the AMHR2-high group. Cellular experiments showed that activation of the AMH-AMHR2 pathway suppressed cell proliferation.
Conclusion: In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH-AMHR2 pathway may suppress cell proliferation.
背景:尽管癌症治疗取得了进展,但非小细胞肺癌(NSCLC)仍是全球癌症相关死亡的主要原因。在几种妇科癌症中,抗苗勒氏管激素受体 2 型(AMHR2)介导 AMH 诱导的生长抑制,并高水平表达。此外,5%-8%的非小细胞肺癌也有AMHR2的高表达,这表明AMH可能会抑制某些肺癌的进展。然而,AMHR2表达的临床意义及其在肺癌中的作用尚未完全明确:方法:对79例NSCLC手术标本进行免疫染色。方法:对79例NSCLC手术标本进行了免疫染色,分析了肺腺癌的癌症基因组图谱RNA-seq数据,并进行了基因本体和基因组富集分析。在细胞实验中,建立了AMHR2-表达的NSCLC细胞系,并研究了重组人AMH蛋白处理AMH-AMHR2通路在细胞增殖中的作用:结果:在肺腺癌组织中,共有13例(16.5%)免疫染色呈阳性;在肺鳞癌组织中未发现阳性信号。利用癌症基因组图谱(The Cancer Genome Atlas)数据进行的基因表达变异分析表明,与细胞周期相关的基因在AMHR2高表达组中表达下调。细胞实验表明,激活 AMH-AMHR2 通路可抑制细胞增殖:结论:在AMHR2高表达的肺腺癌组织中,激活AMH-AMHR2通路可抑制细胞增殖。
{"title":"Anti-Müllerian hormone type II receptor protein expression in non-small cell lung cancer and the effect of AMH/AMHR2 signaling on cancer cell proliferation.","authors":"Yoshika Koinuma, Yoichiro Mitsuishi, Wira Winardi, Moulid Hidayat, Aditya Wirawan, Daisuke Hayakawa, Koichiro Kanamori, Naohisa Matsumoto, Takuo Hayashi, Naoko Shimada, Ken Tajima, Kazuya Takamochi, Fumiyuki Takahashi, Kenji Suzuki, Kazuhisa Takahashi","doi":"10.1111/1759-7714.15309","DOIUrl":"10.1111/1759-7714.15309","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition and is expressed at high levels. Furthermore, 5%-8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers. However, the clinical relevance of AMHR2 expression and its role in lung cancer is not fully clarified.</p><p><strong>Methods: </strong>Immunostaining was performed on 79 surgical specimens of NSCLC. The Cancer Genome Atlas RNA-seq data for lung adenocarcinoma were analyzed, and gene ontology and gene set enrichment analyses were performed. In cellular experiments, AMHR2-overexpressing NSCLC cell lines were established, and the role of the AMH-AMHR2 pathway in cell proliferation with recombinant human AMH protein treatment was examined.</p><p><strong>Results: </strong>A total of 13 cases (16.5%) were positive for immunostaining in lung adenocarcinoma tissues; no positive signals were detected in lung squamous carcinoma tissues. Gene expression variation analysis using The Cancer Genome Atlas data showed that the expression of genes related to the cell cycle was downregulated in the AMHR2-high group. Cellular experiments showed that activation of the AMH-AMHR2 pathway suppressed cell proliferation.</p><p><strong>Conclusion: </strong>In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH-AMHR2 pathway may suppress cell proliferation.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"2090-2099"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma.
Method: A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR-TRC-12002719). Survival data were analyzed in terms of intention-to-treat (ITT) and per-protocol (PP) sets for patients undergoing cisplatin and 5-fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B).
Results: The incidence risk of grade III-IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression-free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X2 = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X2 = 1.25,p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X2 = 0.059, p = 0.866).
Conclusion: Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits.
背景本研究探讨了食管鳞癌患者同时接受不同方案化放疗后巩固维持化疗的意义:设计了一项前瞻性随机对照 III 期临床试验,并在中国临床试验注册中心进行了注册(注册号:ChiCTR-TRC-12002719)。对接受顺铂和5-氟尿嘧啶(PF)治疗(A组)或顺铂和紫杉醇(TP)治疗(B组)的患者的意向治疗组(ITT)和按方案治疗组(PP)的生存数据进行分析:B组III-IV级白细胞减少症的发生风险高于A组(49.2%对25.5%,P=0.012)。1年、2年、3年和5年的生存率分别为83.8%、62.6%、53.1%和41.3%。同期化放疗后的巩固化疗对中位无进展生存期(PFS)(p = 0.95)和总生存期(OS)(p = 0.809)没有益处。根据 ITT 分析,A 组和 B 组的中位无进展生存期分别为 28.6 个月和 30.3 个月(X2 = 0.242,p = 0.623),而中位总生存期分别为 31.0 个月和 50.3 个月(X2 = 1.25,p = 0.263)。在PP分析中,A组和B组的中位PFS分别为28.6个月和30.3个月(P = 0.584),而中位OS分别为31.0个月和50.3个月(P = 0.259)。接受巩固化疗的患者并未显示出明显的OS获益(46.9个月 vs. 38.3个月;X2 = 0.059,p = 0.866):结论:同时接受放化疗的PF和TP方案的PFS和OS相似。结论:PF和TP方案在同时进行化放疗的情况下,PFS和OS相似。
{"title":"The significance of consolidation chemotherapy after concurrent chemoradiotherapy in esophageal squamous cell carcinoma: a randomized controlled phase III clinical trial.","authors":"Qingshan Zhu, Chi Zhang, Zhuoqi Li, Tingwei Ma, Nengchao Wang, Weipeng Liu, Zhijie He, Jing Shen, Tao Wei, Shijie Zhao, Lianjie Feng, Yuan Tian","doi":"10.1111/1759-7714.15424","DOIUrl":"10.1111/1759-7714.15424","url":null,"abstract":"<p><strong>Background: </strong>This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma.</p><p><strong>Method: </strong>A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR-TRC-12002719). Survival data were analyzed in terms of intention-to-treat (ITT) and per-protocol (PP) sets for patients undergoing cisplatin and 5-fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B).</p><p><strong>Results: </strong>The incidence risk of grade III-IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression-free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X<sup>2</sup> = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X<sup>2</sup> = 1.25,p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X<sup>2</sup> = 0.059, p = 0.866).</p><p><strong>Conclusion: </strong>Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"2038-2048"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-09-02DOI: 10.1111/1759-7714.15431
Karin Shimada, Satoshi Takamori, Marina Nakatsuka, Makoto Endoh
An 84-year-old man with a history of progressive interstitial pneumonia presented to our department with lung cancer (cT2aN0M0-IB) in right S6. Moreover, computed tomography revealed progressive diffuse pulmonary ossification in the bilateral lower pulmonary lobes. S6 segmentectomy was performed via video-assisted thoracoscopic surgery. It was difficult to divide the intersegmental plane using a stapler because of severe fibrosis and pulmonary ossification with bone marrow formation. Pulmonary ossification may be an important finding for surgical planning because of severe fibrosis or inflammation associated with severe lung condition. We suggest that the surgical indications and approaches for such cases should be reconsidered because pulmonary ossification can be associated with severe lung conditions.
{"title":"Risks of segmentectomy for interstitial pneumonia with diffuse pulmonary ossification.","authors":"Karin Shimada, Satoshi Takamori, Marina Nakatsuka, Makoto Endoh","doi":"10.1111/1759-7714.15431","DOIUrl":"10.1111/1759-7714.15431","url":null,"abstract":"<p><p>An 84-year-old man with a history of progressive interstitial pneumonia presented to our department with lung cancer (cT2aN0M0-IB) in right S6. Moreover, computed tomography revealed progressive diffuse pulmonary ossification in the bilateral lower pulmonary lobes. S6 segmentectomy was performed via video-assisted thoracoscopic surgery. It was difficult to divide the intersegmental plane using a stapler because of severe fibrosis and pulmonary ossification with bone marrow formation. Pulmonary ossification may be an important finding for surgical planning because of severe fibrosis or inflammation associated with severe lung condition. We suggest that the surgical indications and approaches for such cases should be reconsidered because pulmonary ossification can be associated with severe lung conditions.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"2136-2138"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-09-09DOI: 10.1111/1759-7714.15436
Yunxin Liu, Xiaoyi Feng, Yan Xu, Siyuan Yu, Mengzhao Wang
Ocular metastasis is a rare type of distant metastasis of lung cancer. Limited information is available regarding ocular symptoms, diagnosis, treatment, and prognosis. We reported 16 patients diagnosed with ocular metastasis from lung cancer treated at our hospital from January 1988 to March 2024 and conducted a systematic review of 100 patients retrieved from the PubMed database from January 2014 to December 2023. A pooled analysis was performed using individual-level patient data to generate the hazard ratio (HR) of the association between patient characteristics and overall survival. A total of 116 patients, 100 patients from the literature and 16 patients from our center, diagnosed with ocular metastasis from lung cancer were included in this study. Choroid metastasis was presented in 77 (66.4%) patients and was significantly associated with the onset of lung cancer with ocular symptoms and decreased vision; iris metastasis was significantly associated with small cell lung cancer (SCLC), high intraocular pressure, and ocular pain. Multivariate analyses revealed that males (HR, 2.488; 95% confidence interval [CI], 1.127-5.495), age ≥ 60 years (HR, 3.196; 95% CI, 1.391-7.341), and onset with ocular symptoms (HR, 4.312; 95% CI, 1.675-11.099) were significantly associated with overall survival. For non-SCLC (NSCLC) patients, compared with chemotherapy, targeted therapy (HR, 0.238; 95% CI, 0.087-0.651) and combined therapy (HR, 0.133; 95% CI, 0.017-0.822) have greater therapeutic efficacy. Chemotherapy combined with immunotherapy and targeted therapy are more effective than chemotherapy alone for ocular metastatic NSCLC patients. For patients with targetable mutations, new-generation tyrosine kinase inhibitors (TKIs) are preferred.
{"title":"Clinical manifestation and outcome of lung cancer patients with ocular metastasis: 16 case reports and systematic review.","authors":"Yunxin Liu, Xiaoyi Feng, Yan Xu, Siyuan Yu, Mengzhao Wang","doi":"10.1111/1759-7714.15436","DOIUrl":"10.1111/1759-7714.15436","url":null,"abstract":"<p><p>Ocular metastasis is a rare type of distant metastasis of lung cancer. Limited information is available regarding ocular symptoms, diagnosis, treatment, and prognosis. We reported 16 patients diagnosed with ocular metastasis from lung cancer treated at our hospital from January 1988 to March 2024 and conducted a systematic review of 100 patients retrieved from the PubMed database from January 2014 to December 2023. A pooled analysis was performed using individual-level patient data to generate the hazard ratio (HR) of the association between patient characteristics and overall survival. A total of 116 patients, 100 patients from the literature and 16 patients from our center, diagnosed with ocular metastasis from lung cancer were included in this study. Choroid metastasis was presented in 77 (66.4%) patients and was significantly associated with the onset of lung cancer with ocular symptoms and decreased vision; iris metastasis was significantly associated with small cell lung cancer (SCLC), high intraocular pressure, and ocular pain. Multivariate analyses revealed that males (HR, 2.488; 95% confidence interval [CI], 1.127-5.495), age ≥ 60 years (HR, 3.196; 95% CI, 1.391-7.341), and onset with ocular symptoms (HR, 4.312; 95% CI, 1.675-11.099) were significantly associated with overall survival. For non-SCLC (NSCLC) patients, compared with chemotherapy, targeted therapy (HR, 0.238; 95% CI, 0.087-0.651) and combined therapy (HR, 0.133; 95% CI, 0.017-0.822) have greater therapeutic efficacy. Chemotherapy combined with immunotherapy and targeted therapy are more effective than chemotherapy alone for ocular metastatic NSCLC patients. For patients with targetable mutations, new-generation tyrosine kinase inhibitors (TKIs) are preferred.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"2147-2155"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Inositol-requiring enzyme 1 (IRE1) is an endoplasmic reticulum (ER)-resident transmembrane protein that senses ER stress and mediates an essential arm of the unfolded protein response (UPR). IRE1 reduces ER stress by upregulating the expression of multiple ER chaperones through activation of X-box-binding protein 1 (XBP1). Emerging lines of evidence have revealed that IRE1-XBP1 axis serves as a multipurpose signal transducer during oncogenic transformation and cancer development. In this study, we explore how IRE1-XBP1 signaling promotes chemoresistance in lung cancer.
Methods: The expression patterns of UPR components and MRP1 were examined by Western blot. qRT-PCR was employed to determine RNA expression. The promoter activity was determined by luciferase reporter assay. Chemoresistant cancer cells were analyzed by viability, apoptosis. CUT & Tag (Cleavage under targets and tagmentation)-qPCR analysis was used for analysis of DNA-protein interaction.
Results: Here we show that activation of IRE1α-XBP1 pathway leads to an increase in MDR-related protein 1 (MRP1) expression, which facilitates drug extrusion and confers resistance to cytotoxic chemotherapy. At the molecular level, XBP1-induced c-Myc is necessary for SREBP1 expression, and SREBP1 binds to the MRP1 promoter to directly regulate its transcription.
Conclusions: We conclude that IRE1α-XBP1 had important role in chemoresistance and appears to be a novel prognostic marker for lung cancer.
背景:肌醇需要酶 1(IRE1)是一种内质网(ER)驻留跨膜蛋白,可感知ER压力并介导未折叠蛋白反应(UPR)的重要部分。IRE1 通过激活 X-box 结合蛋白 1 (XBP1),上调多种 ER 合子的表达,从而减轻 ER 压力。新的证据表明,IRE1-XBP1 轴在致癌转化和癌症发展过程中充当着多功能信号转导器的角色。本研究探讨了 IRE1-XBP1 信号如何促进肺癌的化疗耐药性:方法:通过 Western 印迹检测 UPR 成分和 MRP1 的表达模式。荧光素酶报告实验测定启动子活性。化疗耐药癌细胞的存活率和凋亡率进行了分析。CUT & Tag (Cleavage under targets and tagmentation) -qPCR 分析用于分析 DNA 蛋白相互作用:结果:我们在这里发现,IRE1α-XBP1 通路的激活会导致 MDR 相关蛋白 1(MRP1)的表达增加,从而促进药物挤出并产生对细胞毒性化疗的耐药性。在分子水平上,XBP1诱导的c-Myc是SREBP1表达的必要条件,SREBP1与MRP1启动子结合直接调控其转录:我们得出结论:IRE1α-XBP1在化疗耐药性中起着重要作用,似乎是肺癌的一种新型预后标志物。
{"title":"IRE1α-XBP1s axis regulates SREBP1-dependent MRP1 expression to promote chemoresistance in non-small cell lung cancer cells.","authors":"Yuzhou Xu, Feng Gui, Zhe Zhang, Zhongyang Chen, Tiange Zhang, Yunhan Hu, Huijun Wei, Yuchen Fu, Xinde Chen, Zhihao Wu","doi":"10.1111/1759-7714.15442","DOIUrl":"10.1111/1759-7714.15442","url":null,"abstract":"<p><strong>Background: </strong>Inositol-requiring enzyme 1 (IRE1) is an endoplasmic reticulum (ER)-resident transmembrane protein that senses ER stress and mediates an essential arm of the unfolded protein response (UPR). IRE1 reduces ER stress by upregulating the expression of multiple ER chaperones through activation of X-box-binding protein 1 (XBP1). Emerging lines of evidence have revealed that IRE1-XBP1 axis serves as a multipurpose signal transducer during oncogenic transformation and cancer development. In this study, we explore how IRE1-XBP1 signaling promotes chemoresistance in lung cancer.</p><p><strong>Methods: </strong>The expression patterns of UPR components and MRP1 were examined by Western blot. qRT-PCR was employed to determine RNA expression. The promoter activity was determined by luciferase reporter assay. Chemoresistant cancer cells were analyzed by viability, apoptosis. CUT & Tag (Cleavage under targets and tagmentation)-qPCR analysis was used for analysis of DNA-protein interaction.</p><p><strong>Results: </strong>Here we show that activation of IRE1α-XBP1 pathway leads to an increase in MDR-related protein 1 (MRP1) expression, which facilitates drug extrusion and confers resistance to cytotoxic chemotherapy. At the molecular level, XBP1-induced c-Myc is necessary for SREBP1 expression, and SREBP1 binds to the MRP1 promoter to directly regulate its transcription.</p><p><strong>Conclusions: </strong>We conclude that IRE1α-XBP1 had important role in chemoresistance and appears to be a novel prognostic marker for lung cancer.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"2116-2127"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-08-18DOI: 10.1111/1759-7714.15420
Pinar Çağan, Ali Kimiaei, Seyedehtina Safaei, Houssam Eddine Youcefi, Alara Abu Saadeh, Feride Yaman, Özlem Yapıcıer, Cemal Asim Kutlu
Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is a rare pulmonary neoplasm, with less than 150 cases documented in the literature. We report a unique case of BA/CMPT complicated by lymphoid interstitial pneumonia (LIP) in a 55-year-old male with Sjögren's disease. This is the first documented instance of such a comorbidity. Through a systematic review of PubMed, we also summarize the demographic, clinical, radiological, histopathological, and treatment characteristics of CMPT.
{"title":"Bronchiolar adenoma/ciliated muconodular papillary tumor complicated by lymphoid interstitial pneumonia in a patient with Sjögren's disease: A case report and systematic review.","authors":"Pinar Çağan, Ali Kimiaei, Seyedehtina Safaei, Houssam Eddine Youcefi, Alara Abu Saadeh, Feride Yaman, Özlem Yapıcıer, Cemal Asim Kutlu","doi":"10.1111/1759-7714.15420","DOIUrl":"10.1111/1759-7714.15420","url":null,"abstract":"<p><p>Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is a rare pulmonary neoplasm, with less than 150 cases documented in the literature. We report a unique case of BA/CMPT complicated by lymphoid interstitial pneumonia (LIP) in a 55-year-old male with Sjögren's disease. This is the first documented instance of such a comorbidity. Through a systematic review of PubMed, we also summarize the demographic, clinical, radiological, histopathological, and treatment characteristics of CMPT.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"1975-1988"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The relationship between the combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) and prognosis in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) combination therapy with chemotherapy remains unclear. Thus, we investigated prognostic factors, including the COP-NLR, to identify patients who could benefit from the therapeutic efficacy of ICI combination therapy for advanced NSCLC. Furthermore, we evaluated the relationship between the COP-NLR score during ICI combination therapy and treatment response.
Methods: We conducted a retrospective cohort study of 88 patients with NSCLC who initially received ICI combination therapy. The primary outcome was overall survival (OS). The prognostic factors were extracted using the Cox proportional hazards model. The relationship between COP-NLR score at 3 weeks after starting ICI combination therapy and a good response (complete response [CR] and partial response [PR]) to treatment was analyzed using the chi-square test.
Results: The median OS was 15.7 months. In the multivariable analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, distant metastatic sites ≥2, and baseline COP-NLR scores of 1, 2 were extracted as significant poor prognostic factors. The proportion of patients with CR and PR in the 3-week COP-NLR score of 0 group was significantly higher than that in scores of 1, 2 group.
Conclusions: Baseline COP-NLR, ECOG PS, and number of distant metastatic sites were prognostic factors in patients with NSCLC with ICI combination therapy. A lower 3-week COP-NLR was associated with a good response to treatment.
{"title":"Relationship between the combination of platelet count and neutrophil-lymphocyte ratio and prognosis of patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors plus chemotherapy: A retrospective cohort study.","authors":"Saeko Kashimura, Miki Sato, Takahito Inagaki, Masaoki Kin, Ryo Manabe, Sojiro Kusumoto, Atsushi Horiike, Takuya Tsunoda, Mari Kogo","doi":"10.1111/1759-7714.15437","DOIUrl":"10.1111/1759-7714.15437","url":null,"abstract":"<p><strong>Background: </strong>The relationship between the combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) and prognosis in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) combination therapy with chemotherapy remains unclear. Thus, we investigated prognostic factors, including the COP-NLR, to identify patients who could benefit from the therapeutic efficacy of ICI combination therapy for advanced NSCLC. Furthermore, we evaluated the relationship between the COP-NLR score during ICI combination therapy and treatment response.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 88 patients with NSCLC who initially received ICI combination therapy. The primary outcome was overall survival (OS). The prognostic factors were extracted using the Cox proportional hazards model. The relationship between COP-NLR score at 3 weeks after starting ICI combination therapy and a good response (complete response [CR] and partial response [PR]) to treatment was analyzed using the chi-square test.</p><p><strong>Results: </strong>The median OS was 15.7 months. In the multivariable analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, distant metastatic sites ≥2, and baseline COP-NLR scores of 1, 2 were extracted as significant poor prognostic factors. The proportion of patients with CR and PR in the 3-week COP-NLR score of 0 group was significantly higher than that in scores of 1, 2 group.</p><p><strong>Conclusions: </strong>Baseline COP-NLR, ECOG PS, and number of distant metastatic sites were prognostic factors in patients with NSCLC with ICI combination therapy. A lower 3-week COP-NLR was associated with a good response to treatment.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"2049-2060"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We present a unique case of metastatic metaplastic breast carcinoma responding dramatically to immunochemotherapy. A 46-year-old Japanese woman with primary metaplastic carcinoma of the breast, which was immunohistochemically confirmed to be triple-negative breast cancer, underwent radical surgery, followed by adjuvant chemotherapy with an anthracycline and a taxane. Since multiple lung metastases were detected two months post-chemotherapy and the primary site was shown to be PD-L1-positive, the immune checkpoint inhibitor (ICI) pembrolizumab plus gemcitabine/carboplatin was initiated. While the treatment was discontinued after 15 days due to suspected drug-induced pneumonitis, the lung metastases significantly shrank with no development of new lesions for three months. The patient remained alive as of approximately 15 months after the recurrence date. This case highlights the potential of immunochemotherapy in treating metaplastic breast carcinomas.
{"title":"A dramatic response to an immune checkpoint inhibitor plus chemotherapy in a patient with metastatic metaplastic carcinoma of the breast: A case report.","authors":"Yumiko Koi, Wakako Tajiri, Junji Kawasaki, Sayuri Akiyoshi, Hideki Ijichi, Yoshiaki Nakamura, Chinami Koga, Yutaka Koga, Kenichi Taguchi, Eriko Tokunaga","doi":"10.1111/1759-7714.15433","DOIUrl":"10.1111/1759-7714.15433","url":null,"abstract":"<p><p>We present a unique case of metastatic metaplastic breast carcinoma responding dramatically to immunochemotherapy. A 46-year-old Japanese woman with primary metaplastic carcinoma of the breast, which was immunohistochemically confirmed to be triple-negative breast cancer, underwent radical surgery, followed by adjuvant chemotherapy with an anthracycline and a taxane. Since multiple lung metastases were detected two months post-chemotherapy and the primary site was shown to be PD-L1-positive, the immune checkpoint inhibitor (ICI) pembrolizumab plus gemcitabine/carboplatin was initiated. While the treatment was discontinued after 15 days due to suspected drug-induced pneumonitis, the lung metastases significantly shrank with no development of new lesions for three months. The patient remained alive as of approximately 15 months after the recurrence date. This case highlights the potential of immunochemotherapy in treating metaplastic breast carcinomas.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":" ","pages":"2073-2076"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}