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PD-L1 expression in patients with non-small-cell lung cancer is associated with sex and genetic alterations: A retrospective study within the Caucasian population. 非小细胞肺癌患者的 PD-L1 表达与性别和基因改变有关:一项针对高加索人群的回顾性研究。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-06-11 DOI: 10.1111/1759-7714.15336
P Sarova, B Mosleh, S Zehetmayer, F Oberndorfer, J Widder, H Prosch, C Aigner, M Idzko, M A Hoda, D Gompelmann

Background: Programmed cell death-ligand 1 (PD-L1) expression is a well-established biomarker for predicting responses to immune checkpoint inhibitors and certain targeted therapies. As a result, treatment strategies for patients vary based on their PD-L1 expression status. Understanding the clinical features of patients with distinct PD-L1 levels is crucial for personalized treatment approaches.

Methods: Demographic and clinicopathological characteristics of 227 patients (54% male, mean age 67 ± 9.9 years) newly diagnosed with non-small-cell lung cancer (NSCLC) between April 2020 and December 2022 were retrospectively compared among three groups based on the PD-L1 expression: PD-L1 Tumor Proportion Score (TPS) negative, 1-50%, and ≥50%. Logistic regression analysis was performed to evaluate predictors for high PD-L1 expression ≥50%.

Results: PD-L1 expression levels were distributed as follows: negative in 29% of patients, between 1% and 50% in 41%, and greater than 50% (high) in 29%. In comparison to negative PD-L1 expression, low and high PD-L1 expression was associated with female sex (32.9% vs. 52.7% vs. 50.7%, p = 0.031), with the absence of epidermal growth factor receptor (EGFR) mutations (83.6% vs. 91.1% vs. 98.1% p = 0.029), and with the absence of ERBB2 (HER2) tyrosine kinase mutations (90.9% vs. 100% vs. 98.1% p = 0.007), respectively. Age, smoking status, histological subtype, and disease stage showed no significant differences among the three patient groups. In the univariate logistic regression, EGFR mutation appeared to be the only predictor for PD-L1 expression, although it did not reach statistical significance (p = 0.06).

Conclusion: Although sex and genomic alterations are associated with PD-L1 expression in patients with NSCLC, no clinical characteristics seem to predict PD-L1 expression significantly.

背景:程序性细胞死亡配体 1(PD-L1)表达是预测对免疫检查点抑制剂和某些靶向疗法反应的公认生物标志物。因此,患者的治疗策略因其 PD-L1 表达状态而异。了解不同PD-L1水平患者的临床特征对于个性化治疗方法至关重要:方法:回顾性比较了 2020 年 4 月至 2022 年 12 月间新诊断为非小细胞肺癌(NSCLC)的 227 例患者(54% 为男性,平均年龄为 67 ± 9.9 岁)的人口统计学和临床病理学特征:PD-L1肿瘤比例评分(TPS)阴性组、1-50%组和≥50%组。为评估PD-L1高表达≥50%的预测因素,进行了逻辑回归分析:PD-L1表达水平分布如下:29%的患者为阴性,41%的患者表达水平在1%-50%之间,29%的患者表达水平超过50%(高)。与PD-L1的阴性表达相比,PD-L1的低表达和高表达分别与女性性别(32.9% vs. 52.7% vs. 50.7%,p = 0.031)、表皮生长因子受体(EGFR)突变缺失(83.6% vs. 91.1% vs. 98.1% p = 0.029)和ERBB2(HER2)酪氨酸激酶突变缺失(90.9% vs. 100% vs. 98.1% p = 0.007)有关。年龄、吸烟状况、组织学亚型和疾病分期在三组患者中无明显差异。在单变量逻辑回归中,表皮生长因子受体突变似乎是PD-L1表达的唯一预测因子,但未达到统计学意义(p = 0.06):结论:虽然性别和基因组改变与 NSCLC 患者的 PD-L1 表达有关,但临床特征似乎并不能显著预测 PD-L1 的表达。
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引用次数: 0
Survival outcome of esophagectomy and chemoradiotherapy for resectable esophageal squamous cell carcinoma in patients >75 years of age. 对年龄大于 75 岁的可切除食管鳞状细胞癌患者进行食管切除术和放化疗的生存效果。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-06-19 DOI: 10.1111/1759-7714.15329
Shuhei Mayanagi, Masazumi Inoue, Kazunori Tokizawa, Kunihiro Fushiki, Takahiro Tsushima, Tomoya Yokota, Kentaro Yamazaki, Hirofumi Yasui, Yasuhiro Tsubosa

Background: The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery-based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery-based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC.

Methods: Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups.

Results: The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3-year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681-2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3-year OS: surgery 68.1%, dCRT 51.8%, p = 0.117).

Conclusions: There was no clear difference in survival outcome between surgery-based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients.

背景:可切除的局部晚期食管鳞状细胞癌(ESCC)的金标准是手术治疗,但食管切除术或化学放疗是否适合老年患者尚不清楚。这项回顾性研究旨在确定手术治疗与确定性化放疗(dCRT)作为可切除的局部晚期ESCC老年患者初始治疗方法的治疗效果:收集了2011年1月至2020年12月期间434名接受根治性治疗的可切除局部晚期ESCC患者的数据。在年龄大于 75 岁的患者中,49 人接受了根治性食管切除术,26 人接受了 dCRT。比较了手术组和 dCRT 组的生存率:手术组和化疗组的平均年龄分别为 77.3 岁和 78.8 岁。两组的总生存率(OS)差异无统计学意义(3年OS:手术66.2%,dCRT 55.7%,P = 0.236)。OS多变量分析显示,dCRT与手术的危险比为1.229(90%置信区间为0.681-2.217)。各组间的 OS 在任何表现状态下均无差异。对于能够接受氟尿嘧啶和顺铂化疗的患者,手术组的OS往往更好,但差异无统计学意义(3年OS:手术68.1%,dCRT 51.8%,P = 0.117):结论:在老年食管癌的初始治疗中,手术治疗和 dCRT 治疗的生存结果没有明显差异。老年患者可以选择两种治疗方法。
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引用次数: 0
Early patient-reported outcomes after robotic-assisted versus video-assisted thoracoscopic lobectomy. 机器人辅助胸腔镜肺叶切除术与视频辅助胸腔镜肺叶切除术的早期患者报告结果。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-30 DOI: 10.1111/1759-7714.15379
Zihua Lan, Cheng Zeng, Zijie Li, Xin Xia, Aotian Mo, Xianglin Li, Xiaosong Ben, Haiyu Zhou, Cheng Deng, Rixin Chen, Qiuling Shi, Yong Tang, Guibin Qiao

Background: Robotic-assisted thoracoscopic surgery (RATS) can achieve traditional clinical outcomes comparable to those of video-assisted thoracoscopic surgery (VATS). However, patient-reported outcomes (PROs) during the early period after RATS and VATS remain unclear. This study aimed to utilize longitudinal electronic PRO (ePRO) assessments to evaluate symptom burden and functional status between these approaches from patients' perspective.

Methods: This study comprised patients who underwent lobectomy via RATS or VATS for non-small cell lung cancer. We collected multiple-time-point PROs data from the prospective longitudinal study via an ePRO system. Symptom severity and function status were assessed using the perioperative symptom assessment for patients undergoing lung surgery and were analyzed between groups using linear mixed-effects models.

Results: Of the 164 patients, 42 underwent RATS and 122 underwent VATS. After propensity score matching (PSM), 42 RATS and 84 VATS exhibited similar baseline characteristics. During the 7-day postoperative period, participants underwent RATS reported milder pain (p = 0.014), coughing (p < 0.001), drowsiness (p = 0.001), and distress (p = 0.045) compared with those underwent VATS. Moreover, participants in RATS group showed less functional interference with walking (p < 0.001) and general activity (p < 0.001). RATS exhibited a shorter postoperative hospitalization (p = 0.021) but higher hospital cost (p < 0.001). Meanwhile, short-term clinical outcomes of operative time, dissected lymph node stations, chest tube drainage, and postoperative complication rates were comparable.

Conclusion: PROs are important metrics for assessing patients' recovery after lobectomy. Compared with VATS, RATS may induce less symptom burden and better functional status for patients in the early postoperative period.

背景:机器人辅助胸腔镜手术(RATS)可获得与视频辅助胸腔镜手术(VATS)相当的传统临床疗效。然而,RATS 和 VATS 术后早期的患者报告结果(PROs)仍不明确。本研究旨在利用纵向电子PRO(ePRO)评估,从患者的角度评估这两种方法之间的症状负担和功能状态:本研究的对象包括接受 RATS 或 VATS 肺叶切除术的非小细胞肺癌患者。我们通过 ePRO 系统收集了前瞻性纵向研究中的多时间点 PROs 数据。采用肺部手术患者围手术期症状评估方法对症状严重程度和功能状态进行评估,并采用线性混合效应模型对组间数据进行分析:在164名患者中,42人接受了RATS手术,122人接受了VATS手术。经过倾向得分匹配(PSM)后,42 例 RATS 和 84 例 VATS 患者的基线特征相似。在术后 7 天内,接受 RATS 的患者报告的疼痛(p = 0.014)和咳嗽(p 结论:RATS 和 VATS 患者的疼痛和咳嗽症状均较轻:PROs是评估肺叶切除术后患者恢复情况的重要指标。与 VATS 相比,RATS 可在术后早期减轻患者的症状负担,改善患者的功能状态。
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引用次数: 0
Screening for lung cancer using thin-slice low-dose computed tomography in southwestern China: a population-based real-world study. 中国西南地区使用薄层低剂量计算机断层扫描筛查肺癌:一项基于人口的真实世界研究。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-27 DOI: 10.1111/1759-7714.15383
Jiaxuan Wu, Ruicen Li, Huohuo Zhang, Qian Zheng, Wenjuan Tao, Ming Yang, Yuan Zhu, Guiyi Ji, Weimin Li

Objectives: Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low-dose computed tomography (LDCT) screening for the high-risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real-world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick-slice LDCT scanning.

Methods: A total of 29 296 subjects who underwent low-dose thick-slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low-dose thin-slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups.

Results: The positive rate of LDCT screening in the thin-slice scanning group was significantly higher than that in the thick-slice scanning group (20.1% vs. 14.4%, p < 0.001). In addition, the lung cancer detection rate in the thin-slice LDCT screening positive group was significantly higher than that in the thick-slice scanning group (78.0% vs. 52.9%, p < 0.001).

Conclusions: The screening positive rate of low-dose thin-slice CT scanning is higher and more early-stage lung cancer (IA1 stage) can be detected in the screen-positive group.

目的:肺癌是威胁人类生命健康最常见的恶性肿瘤之一。目前,对高危人群进行低剂量计算机断层扫描(LDCT)筛查,以实现肺癌的早诊早治,已成为众多国际权威医学组织推荐的首选方法。为了进一步优化肺癌筛查方法,我们在大样本健康体检人群中开展了一项 LDCT 肺癌筛查的实际研究,比较了薄层和厚层 LDCT 扫描在肺结节和肺癌检出率方面的差异:共纳入华西医院2015年1月至2015年12月接受低剂量厚层CT扫描(厚度5毫米)的29 296例受检者和2018年1月至2018年12月接受低剂量薄层CT扫描(厚度1毫米)的28 058例受检者。对两组的阳性检出率、肺癌检出率、肺癌病理分期、肺癌死亡率进行分析比较:结果:薄层扫描组的 LDCT 筛查阳性率(20.1% 对 14.4%,P)明显高于厚层扫描组:低剂量薄层 CT 扫描的筛查阳性率更高,筛查阳性组能发现更多早期肺癌(IA1 期)。
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引用次数: 0
LncRNA AC100826.1 regulated PLCB1 to promote progression in non-small cell lung cancer. LncRNA AC100826.1调控PLCB1以促进非小细胞肺癌的进展。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-22 DOI: 10.1111/1759-7714.15323
Shenhui Dai, Qiao Wang, Yin Lyu, Zhipeng Chen, Xiucheng Liu, Guoqing Zhao, Hao Zhang

Background: Lung cancer is the most common malignant tumor. In the present study, we identified a long non-coding RNA (lncRNA) AC100826.1 (simplify to Lnc1), which was highly expressed in non-small cell lung cancer (NSCLC) tissues compared with the paracancerous tissues. We also observed the critical role of Lnc1 in regulating the metastasis ability of NSCLC cells.

Methods: RNA sequencing was performed to detect differential expression levels of lncRNAs in NSCLC tissues and its paracancerous tissues. Effects of Lnc1 on cell proliferation, invasion, and migration were determined by CCK-8, transwell and scratch assays. The xenograft experiment confirmed the effect of Lnc1 on NSCLC cells proliferation and migration abilities in vivo. RT-qPCR and western blots were performed to determine the expression levels of mRNAs and proteins.

Results: The expression level of Lnc1 was related to multiple pathological results, knockdown of Lnc1 can inhibit the proliferation and metastasis abilities of NSCLC cells. silencing phospholipase C, β1(PLCB1) can reverse the promoting effects of overexpression Lnc1 on NSCLC cells proliferation and migration abilities. In addition, the Rap1 signaling pathway was implicated in the regulation of Lnc1 in NSCLC metastasis.

Conclusion: Our results suggest that Lnc1 regulated the metastatic ability of NSCLC cells through targeting the PLCB1/Rap1 signal pathway.

背景:肺癌是最常见的恶性肿瘤:肺癌是最常见的恶性肿瘤。在本研究中,我们发现了一种长非编码 RNA(lncRNA)AC100826.1(简化为 Lnc1),与癌旁组织相比,它在非小细胞肺癌(NSCLC)组织中高表达。我们还观察到 Lnc1 在调控 NSCLC 细胞转移能力中的关键作用:方法:通过RNA测序检测NSCLC组织及其癌旁组织中lncRNAs的不同表达水平。Lnc1对细胞增殖、侵袭和迁移的影响通过CCK-8、跨孔实验和划痕实验进行测定。异种移植实验证实了 Lnc1 对 NSCLC 细胞增殖和迁移能力的影响。RT-qPCR 和 Western 印迹检测了 mRNA 和蛋白质的表达水平:结果:Lnc1的表达水平与多种病理结果有关,敲除Lnc1可抑制NSCLC细胞的增殖和转移能力;沉默磷脂酶C,β1(PLCB1)可逆转过表达Lnc1对NSCLC细胞增殖和迁移能力的促进作用。此外,Rap1信号通路也参与了Lnc1在NSCLC转移中的调控:我们的研究结果表明,Lnc1通过靶向PLCB1/Rap1信号通路调控NSCLC细胞的转移能力。
{"title":"LncRNA AC100826.1 regulated PLCB1 to promote progression in non-small cell lung cancer.","authors":"Shenhui Dai, Qiao Wang, Yin Lyu, Zhipeng Chen, Xiucheng Liu, Guoqing Zhao, Hao Zhang","doi":"10.1111/1759-7714.15323","DOIUrl":"10.1111/1759-7714.15323","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most common malignant tumor. In the present study, we identified a long non-coding RNA (lncRNA) AC100826.1 (simplify to Lnc1), which was highly expressed in non-small cell lung cancer (NSCLC) tissues compared with the paracancerous tissues. We also observed the critical role of Lnc1 in regulating the metastasis ability of NSCLC cells.</p><p><strong>Methods: </strong>RNA sequencing was performed to detect differential expression levels of lncRNAs in NSCLC tissues and its paracancerous tissues. Effects of Lnc1 on cell proliferation, invasion, and migration were determined by CCK-8, transwell and scratch assays. The xenograft experiment confirmed the effect of Lnc1 on NSCLC cells proliferation and migration abilities in vivo. RT-qPCR and western blots were performed to determine the expression levels of mRNAs and proteins.</p><p><strong>Results: </strong>The expression level of Lnc1 was related to multiple pathological results, knockdown of Lnc1 can inhibit the proliferation and metastasis abilities of NSCLC cells. silencing phospholipase C, β1(PLCB1) can reverse the promoting effects of overexpression Lnc1 on NSCLC cells proliferation and migration abilities. In addition, the Rap1 signaling pathway was implicated in the regulation of Lnc1 in NSCLC metastasis.</p><p><strong>Conclusion: </strong>Our results suggest that Lnc1 regulated the metastatic ability of NSCLC cells through targeting the PLCB1/Rap1 signal pathway.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082326","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}
引用次数: 0
Optimal approach for diagnosing peripheral lung nodules by combining electromagnetic navigation bronchoscopy and radial probe endobronchial ultrasound. 结合电磁导航支气管镜和径向探头支气管内超声诊断外周肺结节的最佳方法。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-06-17 DOI: 10.1111/1759-7714.15376
Bora Lee, Hee Sang Hwang, Se Jin Jang, Sang Young Oh, Mi Young Kim, Chang-Min Choi, Wonjun Ji

Introduction: Electromagnetic navigation bronchoscopy (ENB) and radial probe endobronchial ultrasound (RP-EBUS) are essential bronchoscopic procedures for diagnosing peripheral lung lesions. Despite their individual advantages, the optimal circumstances for their combination remain uncertain.

Methods: This single-center retrospective study enrolled 473 patients with 529 pulmonary nodules who underwent ENB and/or RP-EBUS biopsies between December 2021 and December 2022. Diagnostic yield was calculated using strict, intermediate, and liberal definitions. In the strict definition, only malignant and specific benign lesions were deemed diagnostic at the time of the index procedure. The intermediate and liberal definitions included additional results from the follow-up period.

Results: The diagnostic yield of the strict definition was not statistically different among the three groups (ENB/Combination/RP-EBUS 63.8%/64.2%/62.6%, p = 0.944). However, the diagnostic yield was superior in the ENB + RP-EBUS group for nodules with a bronchus type II or III and a solid part <20 mm (odds ratio 1.96, 95% confidence interval 1.09-3.53, p = 0.02). In terms of complications, bleeding was significantly higher in the ENB + RP-EBUS group (ENB/Combination/RP-EBUS 3.7% /6.2/0.6%, p = 0.002), but no major adverse event was observed.

Conclusion: The combination of ENB and RP-EBUS enhanced the diagnostic yield for nodules with bronchus type II or III and solid part <20 mm, despite a slightly elevated risk of bleeding. Careful patient selection based on nodule characteristics is important to benefit from this combined approach.

导言:电磁导航支气管镜(ENB)和径向探头支气管内超声(RP-EBUS)是诊断肺部外周病变必不可少的支气管镜检查方法。尽管二者各有优势,但二者结合的最佳情况仍不确定:这项单中心回顾性研究纳入了 2021 年 12 月至 2022 年 12 月期间接受 ENB 和/或 RP-EBUS 活检的 473 例 529 个肺结节患者。采用严格、中间和宽松定义计算诊断率。在严格定义中,只有恶性病变和特定良性病变在进行索引手术时才被视为具有诊断意义。中级定义和自由定义包括随访期间的其他结果:严格定义的诊断率在三组之间没有统计学差异(ENB/Combination/RP-EBUS 63.8%/64.2%/62.6%,P = 0.944)。然而,ENB+RP-EBUS 组对具有 II 型或 III 型支气管和实心部分的结节的诊断率更高:ENB和RP-EBUS联合使用可提高对支气管II型或III型和实性部分的结节的诊断率
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引用次数: 0
Lipocalin-2 as a prognostic biomarker and its association with systemic inflammation in small cell lung cancer. 作为预后生物标志物的脂联素-2及其与小细胞肺癌全身炎症的关系
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-06-17 DOI: 10.1111/1759-7714.15389
Se-Il Go, Jung Wook Yang, Woo Je Lee, Eun Jeong Jeong, Sungwoo Park, Gyeong-Won Lee

Background: Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin-2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored.

Methods: We retrospectively analyzed 191 patients with SCLC (72 with limited-stage [LD] and 119 with extensive-stage) treated using platinum-based chemotherapy. Lipocalin-2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin-2 and neutrophil-to-lymphocyte ratio (NLR) were determined using time-dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia.

Results: In LD-SCLC, high lipocalin-2 expression was associated with worse progression-free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin-2 expression. Patients were stratified into three prognostic groups by combining lipocalin-2 with NLR: low lipocalin-2/low NLR, high lipocalin-2/low NLR or low lipocalin-2/high NLR, and high lipocalin-2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin-2 with the pectoralis muscle index. High lipocalin-2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin-2 in extensive-stage SCLC.

Conclusions: High lipocalin-2 expression is potentially associated with poorer survival in LD-SCLC. Combining lipocalin-2 with other inflammation-related markers could improve prognostic stratification.

背景:全身性炎症被认为是导致小细胞肺癌(SCLC)进展的原因之一,但其潜在的关系仍不清楚。脂联素-2是一种潜在的炎症生物标志物,已与多种癌症有关联,但其在SCLC中的预后价值尚未得到充分探讨:我们回顾性分析了191例接受铂类化疗的SCLC患者(72例为局限期[LD],119例为广泛期)。采用免疫组化方法评估了脂联素-2的表达。脂联素-2和中性粒细胞与淋巴细胞比值(NLR)的最佳临界值是通过时间依赖性接收者操作特征曲线分析确定的。胸肌指数用于评估肌肉疏松症:结果:在LD-SCLC中,与低脂钙蛋白-2表达相比,高脂钙蛋白-2表达与较差的无进展生存期(PFS;中位数:7.0个月 vs. 15.9个月,p = 0.015)和总生存期(OS;中位数:12.9个月 vs. 30.3个月,p = 0.035)相关。结合脂钙蛋白-2和NLR,将患者分为三个预后组:低脂钙蛋白-2/低NLR、高脂钙蛋白-2/低NLR或低脂钙蛋白-2/高NLR和高脂钙蛋白-2/高NLR(中位PFS:17.3个月 vs. 11.0个月 vs. 6.3个月,p = 0.004;中位OS:30.5个月 vs. 17.3个月,p = 0.005;中位OS:30.5个月 vs. 17.3个月,p = 0.005):30.5 个月 vs. 17.3 个月 vs. 8.6 个月,p = 0.002)。将脂联素-2与胸肌指数相结合,也能观察到类似的趋势。高脂钙蛋白-2表达也与较低的完全缓解率有关(18.9% vs. 34.3%,p = 0.035)。在广泛期SCLC中未发现脂联素-2对预后有明显影响:结论:脂联素-2的高表达可能与LD-SCLC较差的生存率有关。将脂联素-2与其他炎症相关标志物相结合可改善预后分层。
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引用次数: 0
Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival. 与恶性间皮瘤存活率相关的基因组和 T 细胞群生物标志物。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-27 DOI: 10.1111/1759-7714.15326
Muwen Nie, Zhao Sun, Ningning Li, Liangrui Zhou, Shuchun Wang, Mingming Yuan, Rongrong Chen, Lin Zhao, Ji Li, Chunmei Bai

Background: Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM.

Methods: DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023.

Results: Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (<6.637), lower evenness (<0.028), or higher clonality (≥0.194) according to baseline tumor tissue TCR indexes, demonstrated poorer OS. Furthermore, patients with TP53, CDKN2A, or CDKN2B variants and those with a lower evenness (<0.030) in baseline tumor tissue showed worse immunotherapy efficacy. The present study is the first to identify five special TCR Vβ-Jβ rearrangements associated with MM immunotherapy efficacy.

Conclusions: The present study reported the largest-scale genomic landscape and TCR repertoire of MM in Chinese patients and identified genomic and TCR biomarkers for the prognosis and immunotherapy efficacy in MM. The study results might provide new insights for prospective MM trials using specific genes, TCR indexes, and TCR clones as biomarkers and offer a reference for future antitumor drugs based on TCR-specific clones.

背景:恶性间皮瘤(MM)是一种极为罕见的肿瘤,由于有效治疗手段有限,其预后较差。免疫疗法已成为治疗恶性间皮瘤的一种新方法,但只有不到 40% 的患者从中获益。因此,有必要找出准确有效的生物标志物,以预测MM的总生存率(OS)和免疫疗法的疗效:方法:根据86名中国患者的数据,采用DNA测序来确定基因组图谱。T细胞受体(TCR)测序用于描述2016年10月至2023年4月期间28名患者的MM TCR基因组特征:结果:在基因组水平上存在TP53、NF2或CDKN2A变异的患者,以及表现出较低香农指数的患者(结论:这些患者的基因组水平较低:本研究报告了中国MM患者最大规模的基因组图谱和TCR谱系,并确定了影响MM预后和免疫治疗疗效的基因组和TCR生物标志物。研究结果可能为使用特定基因、TCR指数和TCR克隆作为生物标志物的前瞻性MM试验提供新的见解,并为未来基于TCR特异性克隆的抗肿瘤药物提供参考。
{"title":"Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival.","authors":"Muwen Nie, Zhao Sun, Ningning Li, Liangrui Zhou, Shuchun Wang, Mingming Yuan, Rongrong Chen, Lin Zhao, Ji Li, Chunmei Bai","doi":"10.1111/1759-7714.15326","DOIUrl":"10.1111/1759-7714.15326","url":null,"abstract":"<p><strong>Background: </strong>Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM.</p><p><strong>Methods: </strong>DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023.</p><p><strong>Results: </strong>Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (<6.637), lower evenness (<0.028), or higher clonality (≥0.194) according to baseline tumor tissue TCR indexes, demonstrated poorer OS. Furthermore, patients with TP53, CDKN2A, or CDKN2B variants and those with a lower evenness (<0.030) in baseline tumor tissue showed worse immunotherapy efficacy. The present study is the first to identify five special TCR Vβ-Jβ rearrangements associated with MM immunotherapy efficacy.</p><p><strong>Conclusions: </strong>The present study reported the largest-scale genomic landscape and TCR repertoire of MM in Chinese patients and identified genomic and TCR biomarkers for the prognosis and immunotherapy efficacy in MM. The study results might provide new insights for prospective MM trials using specific genes, TCR indexes, and TCR clones as biomarkers and offer a reference for future antitumor drugs based on TCR-specific clones.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155628","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}
引用次数: 0
Is wedge resection equivalent to segmentectomy in pathological stage IA (≤2 cm) non-small cell lung cancers? 对于病理分期为 IA 期(≤2 厘米)的非小细胞肺癌,楔形切除术是否等同于分段切除术?
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-29 DOI: 10.1111/1759-7714.15377
Zhirong Zhang, Feng Li, Shuo Chen, Bin Hu

Background: Sublobar resection (wedge resection and segmentectomy) has been established as an oncologically equivalent option to lobectomy for early-stage patients with non-small cell lung cancer (NSCLC) ≤ 2 cm. However, the optimal approach of sublobar resection remains subject to debate. In the present study we aimed to compare the oncological outcomes of wedge resection and segmentectomy in these patients.

Methods: We identified patients with pT1a-bN0M0 NSCLC who underwent wedge resection and segmentectomy from the Surveillance, Epidemiology, and End Results database between 2010 and 2020. A Cox regression model and propensity-score matching (PSM) analysis were used. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method.

Results: A total of 4190 patients met our selection criteria, including wedge resection in 3137 and segmentectomy in 1053. Patients undergoing wedge resection were less likely to have total lymph nodes resected (4 vs. 7, p < 0.001). Before PSM, patients undergoing segmentectomy had a higher 5-year OS rate (87.75% vs. 82.72%; p = 0.0023), while exhibiting a similar LCSS rate (93.45% vs. 92.73%; p = 0.32). After PSM, segmentectomy consistently demonstrated significantly better OS and there was no statistically significant difference in LCSS. Analysis of causes of death revealed that a higher incidence of deaths related to other causes among patients undergoing wedge resection compared to those undergoing segmentectomy.

Conclusions: Both wedge resection and segmentectomy yield comparable oncological outcomes for patients with NSCLC ≤ 2 cm, although segmentectomy exhibits superior OS due to less death related to other causes.

背景:对于≤2厘米的早期非小细胞肺癌(NSCLC)患者,肺叶下切除术(楔形切除术和肺段切除术)在肿瘤学上与肺叶切除术具有同等疗效。然而,叶下切除术的最佳方法仍存在争议。本研究旨在比较楔形切除术和分段切除术对这些患者的肿瘤治疗效果:我们从 "监测、流行病学和最终结果 "数据库中确定了2010年至2020年间接受楔形切除术和分段切除术的pT1a-bN0M0 NSCLC患者。研究采用了 Cox 回归模型和倾向分数匹配 (PSM) 分析。采用卡普兰-梅耶法比较了总生存期(OS)和肺癌特异性生存期(LCSS):共有 4190 例患者符合我们的选择标准,其中楔形切除术 3137 例,肺段切除术 1053 例。接受楔形切除术的患者总淋巴结被切除的几率较低(4 对 7,P 结论:楔形切除术和分段切除术均可使患者的淋巴结被切除:对于≤2厘米的NSCLC患者来说,楔形切除术和分段切除术的肿瘤治疗效果相当,但分段切除术由于与其他原因相关的死亡较少而显示出更优越的OS。
{"title":"Is wedge resection equivalent to segmentectomy in pathological stage IA (≤2 cm) non-small cell lung cancers?","authors":"Zhirong Zhang, Feng Li, Shuo Chen, Bin Hu","doi":"10.1111/1759-7714.15377","DOIUrl":"10.1111/1759-7714.15377","url":null,"abstract":"<p><strong>Background: </strong>Sublobar resection (wedge resection and segmentectomy) has been established as an oncologically equivalent option to lobectomy for early-stage patients with non-small cell lung cancer (NSCLC) ≤ 2 cm. However, the optimal approach of sublobar resection remains subject to debate. In the present study we aimed to compare the oncological outcomes of wedge resection and segmentectomy in these patients.</p><p><strong>Methods: </strong>We identified patients with pT1a-bN0M0 NSCLC who underwent wedge resection and segmentectomy from the Surveillance, Epidemiology, and End Results database between 2010 and 2020. A Cox regression model and propensity-score matching (PSM) analysis were used. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method.</p><p><strong>Results: </strong>A total of 4190 patients met our selection criteria, including wedge resection in 3137 and segmentectomy in 1053. Patients undergoing wedge resection were less likely to have total lymph nodes resected (4 vs. 7, p < 0.001). Before PSM, patients undergoing segmentectomy had a higher 5-year OS rate (87.75% vs. 82.72%; p = 0.0023), while exhibiting a similar LCSS rate (93.45% vs. 92.73%; p = 0.32). After PSM, segmentectomy consistently demonstrated significantly better OS and there was no statistically significant difference in LCSS. Analysis of causes of death revealed that a higher incidence of deaths related to other causes among patients undergoing wedge resection compared to those undergoing segmentectomy.</p><p><strong>Conclusions: </strong>Both wedge resection and segmentectomy yield comparable oncological outcomes for patients with NSCLC ≤ 2 cm, although segmentectomy exhibits superior OS due to less death related to other causes.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173817","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}
引用次数: 0
Risk factors for severe immune-related pneumonitis after nivolumab plus ipilimumab therapy for non-small cell lung cancer. 尼妥珠单抗加伊匹单抗治疗非小细胞肺癌后出现严重免疫相关性肺炎的风险因素。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2024-07-01 Epub Date: 2024-06-03 DOI: 10.1111/1759-7714.15385
Toshiyuki Sumi, Motoki Sekikawa, Yuta Koshino, Daiki Nagayama, Yuta Nagahisa, Keigo Matsuura, Naoki Shijubou, Koki Kamada, Keito Suzuki, Takumi Ikeda, Haruhiko Michimata, Hiroki Watanabe, Yuichi Yamada, Koichi Osuda, Yusuke Tanaka, Hirofumi Chiba

Background: The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population.

Methods: We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results.

Results: Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm).

Conclusion: Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

背景:抗CTLA-4抗体(ipilimumab)加抗程序性细胞死亡1抗体(nivolumab)治疗晚期非小细胞肺癌(NSCLC)的疗效受到严重免疫相关不良事件风险升高的阻碍。然而,我们对接受这种联合疗法的 NSCLC 患者的原有纤维化、肺气肿变化和客观指标之间的关联性了解有限,而这些都是预测 NSCLC 患者严重肺炎的因素。因此,我们在日本人群中回顾性地调查了这些关联,包括开始治疗前的总体肿瘤负荷:我们重点研究了已存在间质性肺病(ILD)的患者(n = 76),以确定严重肺炎的预测因素。变量包括年龄、性别、吸烟状况、程序性细胞死亡配体 1 表达、总体肿瘤负荷、胸部计算机断层扫描证实的纤维化、血清标记物和呼吸功能测试结果:结果:鳞状细胞癌、纤维化、一氧化碳弥散能力(%DLCO)低和表面活性蛋白 D(SP-D)水平高的患者更易患重症肺炎。值得注意的是,鳞状细胞癌、基线%DLCO和SP-D水平是重要的风险因素。我们的研究结果表明,肿瘤负荷(≥85 毫米)在预测重症肺炎方面没有意义,这强调了原有 ILD 的重要性。相反,在没有先期纤维化的病例中,重症肺炎与%DLCO或SP-D水平无关(分别为93.2%对91.9%和63.3对40.9纳克/毫升),而且在总体肿瘤负荷较大的患者中更为常见(97.5对70.0毫米):结论:对于接受伊匹单抗加尼伐单抗治疗的鳞状细胞癌、高SP-D水平或低%DLCO患者,警惕监测和早期干预至关重要。
{"title":"Risk factors for severe immune-related pneumonitis after nivolumab plus ipilimumab therapy for non-small cell lung cancer.","authors":"Toshiyuki Sumi, Motoki Sekikawa, Yuta Koshino, Daiki Nagayama, Yuta Nagahisa, Keigo Matsuura, Naoki Shijubou, Koki Kamada, Keito Suzuki, Takumi Ikeda, Haruhiko Michimata, Hiroki Watanabe, Yuichi Yamada, Koichi Osuda, Yusuke Tanaka, Hirofumi Chiba","doi":"10.1111/1759-7714.15385","DOIUrl":"10.1111/1759-7714.15385","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population.</p><p><strong>Methods: </strong>We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results.</p><p><strong>Results: </strong>Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm).</p><p><strong>Conclusion: </strong>Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199130","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}
引用次数: 0
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Thoracic Cancer
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