Lung Cancer最新文献_第10页

Immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer patients with preexisting pulmonary emphysema or interstitial lung abnormalities 免疫检查点抑制剂诱导的非小细胞肺癌患者既往存在肺气肿或间质性肺异常的间质性肺疾病

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-07 DOI: 10.1016/j.lungcan.2025.108831

Xi Chen , Caijuan Huan , Piao Yang , Mengye He , Ruiping Wang , Jianying Zhou , Jianya Zhou

Background

Immune checkpoint inhibitor-induced interstitial lung disease (ICI-ILD) is a serious adverse event. While interstitial lung abnormalities (ILA) are known risk factors, the role of preexisting pulmonary emphysema remains controversial.

Patients and methods

We enrolled patients with advanced or recurrent NSCLC who received anti-PD-1 antibody at our institution between October 2020 and October 2022. Clinical characteristics, radiographic features, time of onset, and outcomes of ICI-ILD were compared between patients with preexisting emphysema and/or ILA and those without these conditions.

Results

Among 757 patients, the overall incidence of ICI-ILD was 10.4 %. The incidence in patients with emphysema alone was significantly higher than in those without emphysema or ILA (14.1 % vs. 4.4 %, P < 0.001). The incidence in patients with ILA alone showed a trend toward higher than in those without both conditions (10.7 % vs. 4.4 %, P = 0.054). Notably, a numerically higher incidence of ICI-ILD was observed in patients with severe emphysema (E score ≥ 3; 31.3 % vs. E score = 1–2; 14.7 %, P = 0.072) and in those with baseline honeycombing compared to other ILA subtypes (41.7 % vs. 13.9 %, P = 0.056). Moreover, the presence of baseline extensive ILA was associated with a significantly higher incidence than limited ILA (42.3 % vs. 9.9 %, P < 0.001). Multivariate analysis identified preexisting emphysema (Odds Ratio [OR], 2.81; 95 % CI, 1.60–4.92; P < 0.001), preexisting ILA (OR, 1.98; 95 % CI, 1.13–3.49; P = 0.018), age (OR, 1.04; 95 % CI, 1.01–1.08; P = 0.008), and prior thoracic radiotherapy (OR, 4.10; 95 % CI, 2.12–7.94; P < 0.001) as independent risk factors for ICI-ILD.

Conclusion

Preexisting emphysema or ILA significantly increases the risk of ICI-ILD in NSCLC patients. Close monitoring is warranted, particularly in patients with severe emphysema, honeycombing, or extensive ILA.

背景：免疫检查点抑制剂诱导的间质性肺疾病（ICI-ILD）是一种严重的不良事件。虽然间质性肺异常（ILA）是已知的危险因素，但先前存在的肺气肿的作用仍然存在争议。患者和方法：我们招募了2020年10月至2022年10月期间在我们机构接受抗pd -1抗体治疗的晚期或复发性非小细胞肺癌患者。比较已有肺气肿和/或ILA患者与无这些疾病患者的临床特征、影像学特征、发病时间和ICI-ILD结局。结果：757例患者中，ICI-ILD的总发生率为10.4%。单独有肺气肿的患者的发病率明显高于无肺气肿或ILA的患者（14.1% vs. 4.4%）。结论：既往存在的肺气肿或ILA显著增加非小细胞肺癌患者ICI-ILD的风险。密切监测是必要的，特别是在严重肺气肿、蜂窝状或广泛的ILA患者中。

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引用次数: 0

Treatment outcomes in patients with stage IV large cell neuroendocrine carcinoma: a nationwide registry study IV期大细胞神经内分泌癌患者的治疗结果：一项全国性登记研究

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-07 DOI: 10.1016/j.lungcan.2025.108830

Frank W.J. Heijboer , Jules L. Derks , Francien H. van Nederveen , Lisa M. Hillen , Michael A. den Bakker , Teodora Radonic , Ronald A.M. Damhuis

Introduction

Overall survival (OS) of patients with stage IV large cell neuroendocrine carcinoma (LCNEC) is poor and optimal systemic treatment is unknown. Here, we describe clinical outcomes per treatment strategy of patients with stage IV LCNEC, including stratification by immunohistochemical (IHC) protein RB1 (pRb) status.

Methods

Clinical data were obtained from all patients with LCNEC (2019–2022) in the Netherlands Cancer Registry (NCR). Central pathology review and IHC pRb staining were performed when tumor material was available. OS was calculated from time of diagnosis of stage IV until death, last OS update was April 2024.

Results

In total 269/530 patients (51 %) received systemic treatment, and 132 samples were eligible for pathology review. In 88/132 (67 %) the diagnosis LCNEC was confirmed (other diagnoses: SCLC (34 %), NSCLC NOS (34 %)). The median OS of all panel-reviewed LCNEC patients was 7.4 months. Patients treated with chemo-immunotherapy had a numerically, but not statistically significant different survival compared to chemotherapy (median OS 9.6 months versus OS of 6.5 months; HR 0.71, 95 % CI 0.42–1.2). This was different from the real-world LCNEC patients, where a benefit of immunotherapy was observed (median OS 10.7 months versus OS of 6.7 months; HR 0.53, 95 % CI 0.4–0.72).

Conclusion

In real-world half of patients with stage IV LCNEC do not receive systemic treatment. Accurate diagnosing LCNEC is challenging and therefore introduces bias (i.e. other diagnoses as SCLC instead of LCNEC) in real-world cohorts, which in turn has impact on analysis of treatment outcomes. Patients with panel-reviewed LCNEC have a poor prognosis and no statistically significant improvement was observed with chemo-immunotherapy.

IV期大细胞神经内分泌癌（LCNEC）患者的总生存期（OS）较差，最佳全身治疗尚不清楚。在这里，我们描述了IV期LCNEC患者的每个治疗策略的临床结果，包括免疫组织化学（IHC）蛋白RB1 （pRb）状态的分层。方法从荷兰癌症登记处（NCR）的所有LCNEC患者（2019-2022）中获得临床数据。当肿瘤材料可用时，进行中心病理检查和免疫组化pRb染色。OS计算时间为IV期诊断至死亡，最后一次OS更新时间为2024年4月。结果530例患者中有269例（51% %）接受了全身治疗，132例符合病理检查条件。88/132（67 %）确诊LCNEC(其他诊断：SCLC（34 %),NSCLC NOS(34 %)）。所有经小组审查的LCNEC患者的中位OS为7.4 个月。与化疗相比，接受化疗免疫治疗的患者的生存期在数字上有显著差异，但在统计学上没有显著差异（中位OS 9.6 个月对6.5 个月；HR 0.71, 95 % CI 0.42-1.2）。这与现实世界的LCNEC患者不同，后者观察到免疫治疗的益处（中位OS为10.7 个月，而OS为6.7 个月；HR为0.53,95% % CI为0.4-0.72）。结论：在现实世界中，有一半的IV期LCNEC患者没有接受全身治疗。准确诊断LCNEC具有挑战性，因此在现实世界的队列中会引入偏倚（即其他诊断为SCLC而不是LCNEC），这反过来又会影响治疗结果的分析。经小组审查的LCNEC患者预后较差，化疗免疫治疗没有统计学意义上的显著改善。

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引用次数: 0

MAGELLAN arms B1 and B3: Durvalumab plus chemotherapy with and without oleclumab in treatment-naïve metastatic non-small-cell lung cancer MAGELLAN组B1和B3: Durvalumab加化疗伴或不伴oleclumab治疗treatment-naïve转移性非小细胞肺癌。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-07 DOI: 10.1016/j.lungcan.2025.108834

Byoung Chul Cho , Chaiyut Charoentum , Dong-Wan Kim , Cheng-Ta Yang , Rafal Dziadziuszko , Sarayut Lucien Geater , Helen Mann , Banafsheh Afshar-Imani , Pavlo Lyfar , James Chih-Hsin Yang , Sandip Pravin Patel

Objectives

Standard-of-care therapies for metastatic non-small-cell lung cancer (mNSCLC) have mixed outcomes that remain unsatisfactory. Durvalumab (anti-PD-L1) plus oleclumab (anti-CD73) might provide a synergistic antitumor effect by antagonizing separate immune pathways. We report safety, efficacy, pharmacokinetics, and immunogenicity findings of durvalumab + chemotherapy ± oleclumab as first-line treatment of mNSCLC from Arms B1 and B3 in the phase 1B MAGELLAN (NCT03819465) study.

Methods

In Cohort B, treatment-naïve adults with histologically/cytologically confirmed mNSCLC and PD-L1 expression on < 50 % tumor cells were eligible. Patients received investigator’s choice of chemotherapy plus 1500 mg durvalumab three-weekly (Q3W) for four cycles and durvalumab Q4W thereafter in Arm B1, with addition of 2250 mg oleclumab Q3W for four cycles and 3000 mg Q4W thereafter in Arm B3. Primary endpoint was safety and tolerability; key secondary endpoint was efficacy by investigator-assessed objective response rate (ORR; RECIST v1.1).

Results

Patient demographics and disease characteristics were generally consistent between arms. All but one patient experienced treatment-emergent adverse events (AEs). Grade 3 or 4 AEs and AEs leading to discontinuation occurred in 14/33 (42.4 %) and 3/33 (9.1 %) patients in Arm B1 and 18/32 (56.3 %) and 6/32 (18.8 %) patients in Arm B3. No treatment-related deaths occurred in Arm B1; one (3.1 %) fatal AE of unknown cause was deemed possibly related to both durvalumab and oleclumab by the investigator in Arm B3. ORR was 36.4 % (95 % CI, 20.4–54.9) and 21.9 % (95 % CI, 9.3–40.0) in Arms B1 and B3, respectively − all partial responses. Median duration of response was 11.8 months (95 % CI, 3.2–26.6) and 8.8 months (95 % CI, 2.3–not calculable), respectively.

Conclusion

No new safety signals were identified for durvalumab + chemotherapy ± oleclumab in patients with mNSCLC and PD-L1 expression < 50 %. The lack of meaningful efficacy improvements limits potential further development of this combination in this disease setting.

目的：转移性非小细胞肺癌（mNSCLC）的标准治疗结果好坏参半，仍然不令人满意。Durvalumab（抗pd - l1）和oleclumab（抗cd73）可能通过拮抗不同的免疫途径提供协同抗肿瘤作用。我们在1B期MAGELLAN （NCT03819465）研究中报告durvalumab +化疗±oleclumab作为B1和B3组mNSCLC一线治疗的安全性、有效性、药代动力学和免疫原性结果。方法：在队列B中，treatment-naïve成人组织学/细胞学证实的mNSCLC和PD-L1表达结果：两组患者人口统计学和疾病特征基本一致。除一名患者外，所有患者均经历了治疗后出现的不良事件（ae）。B1组14/33（42.4%）和3/33（9.1%）患者发生3级或4级ae， B3组18/32（56.3%）和6/32（18.8%）患者发生ae导致停药。B1组未发生治疗相关死亡；在B3组中，研究者认为1例（3.1%）原因不明的致死性AE可能与durvalumab和oleclumab相关。B1组和B3组的ORR分别为36.4% （95% CI, 20.4-54.9）和21.9% (95% CI, 9.3-40.0)，均为部分缓解。中位反应持续时间分别为11.8个月（95% CI, 3.2-26.6）和8.8个月（95% CI， 2.3-无法计算）。结论：在PD-L1表达的mNSCLC患者中，durvalumab +化疗±oleclumab未发现新的安全性信号

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引用次数: 0

The immune desert tumor microenvironment in Thoracic SMARCA4-deficient undifferentiated tumors: spatial distribution characteristics and prognostic significance 胸椎smarca4缺失未分化肿瘤的免疫荒漠肿瘤微环境：空间分布特征及预后意义

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-04 DOI: 10.1016/j.lungcan.2025.108817

Xiaotao Wang , Wenwen Shi , Yang Xiao , Haoyu Wang , Huiyu Si , Yan Kang , Jiming Si , Yuanhua Liu , Shenglei Li , Jianjun Jin

Introduction

Thoracic SMARCA4-Deficient Undifferentiated Tumors (SMARCA4-UT) are highly aggressive malignancies with poor prognosis. There is currently no standardized treatment strategy. We aimed to investigate the characteristics of the tumor immune microenvironment (TIME) in SMARCA4-UT, and evaluate the impact of TIME on treatment efficacy and prognosis.

Methods

Multiplex immunofluorescence staining was performed on tumor tissue specimens from 29 SMARCA4-UT cases and 25 SMARCA4-intact non-small cell lung cancer (SMARCA4-iNSCLC) cases to quantify the density, proportion, and spatial proximity of CD8⁺ T cells, M2 macrophages, neutrophils, FOXP3⁺ cells, and IFNα⁺ cells within the immune landscape, and to assess their associations with treatment efficacy and prognosis.

Results

Lower infiltration of CD8⁺T cells and IFNα⁺ cells, but higher infiltration of M2 macrophages in the overall immune landscape, was observed in SMARCA4-UT compared with SMARCA4–iNSCLC (P < 0.05). Patients with higher CD8⁺T cells and IFNα⁺ cells infiltration had longer overall survival (OS) following immunotherapy. Multivariate Cox regression identified high CD8⁺T cell infiltration as an independent protective prognostic factor in the SMARCA4-UT group (HR = 0.204, P = 0.017). Within the TIME of SMARCA4-UT, CD8⁺T cells, FOXP3⁺ cells, and IFNα⁺ cells were located in closer proximity to M2 macrophages. The distance between individual M2 macrophages was significantly shorter; conversely, neutrophils were positioned further away from M2 macrophages (P < 0.05). Further, greater distance between M2 macrophages and CD8⁺T cells correlated with better prognosis (HR = 0.834, P = 0.047) and a significantly longer median OS (P = 0.016).

Conclusion

The TIME of SMARCA4-UT is characterized by an immune-desert phenotype, and higher CD8⁺T cells infiltration is associated with improved immunotherapeutic efficacy. Spatial proximity between M2 macrophages and multiple immune cell subsets within the TIME of SMARCA4-UT is markedly increased.

胸部smarca4缺陷未分化肿瘤（SMARCA4-UT）是一种预后不良的高侵袭性恶性肿瘤。目前尚无标准化的治疗策略。我们旨在探讨SMARCA4-UT中肿瘤免疫微环境（TIME）的特点，并评价TIME对治疗疗效和预后的影响。方法对29例SMARCA4-UT和25例smarca4完整非小细胞肺癌（SMARCA4-iNSCLC）患者的肿瘤组织标本进行多元免疫荧光染色，定量测定免疫景观中CD8+ T细胞、M2巨噬细胞、中性粒细胞、FOXP3+细胞和IFNα+细胞的密度、比例和空间接近度，并评估其与治疗效果和预后的关系。结果与SMARCA4-iNSCLC相比，SMARCA4-UT中CD8+T细胞和IFNα+细胞的浸润率较低，M2巨噬细胞的浸润率较高（P < 0.05）。CD8+T细胞和IFNα+细胞浸润较高的患者在免疫治疗后总生存期（OS）更长。多因素Cox回归发现，高CD8+T细胞浸润是SMARCA4-UT组患者独立的保护性预后因素（HR = 0.204, P = 0.017）。在SMARCA4-UT时间内，CD8+T细胞、FOXP3+细胞和IFNα+细胞更靠近M2巨噬细胞。M2巨噬细胞之间的距离明显缩短；相反，中性粒细胞的位置远离M2巨噬细胞（P < 0.05）。M2巨噬细胞与CD8+T细胞距离越远，预后越好（HR = 0.834, P = 0.047），中位OS越长（P = 0.016）。结论SMARCA4-UT的TIME具有免疫荒漠表型，CD8+T细胞浸润增加与免疫治疗效果提高有关。SMARCA4-UT时间内M2巨噬细胞与多个免疫细胞亚群之间的空间接近性明显增加。

{"title":"The immune desert tumor microenvironment in Thoracic SMARCA4-deficient undifferentiated tumors: spatial distribution characteristics and prognostic significance","authors":"Xiaotao Wang , Wenwen Shi , Yang Xiao , Haoyu Wang , Huiyu Si , Yan Kang , Jiming Si , Yuanhua Liu , Shenglei Li , Jianjun Jin","doi":"10.1016/j.lungcan.2025.108817","DOIUrl":"10.1016/j.lungcan.2025.108817","url":null,"abstract":"<div><h3>Introduction</h3><div>Thoracic SMARCA4-Deficient Undifferentiated Tumors (SMARCA4-UT) are highly aggressive malignancies with poor prognosis. There is currently no standardized treatment strategy. We aimed to investigate the characteristics of the tumor immune microenvironment (TIME) in SMARCA4-UT, and evaluate the impact of TIME on treatment efficacy and prognosis.</div></div><div><h3>Methods</h3><div>Multiplex immunofluorescence staining was performed on tumor tissue specimens from 29 SMARCA4-UT cases and 25 SMARCA4-intact non-small cell lung cancer (SMARCA4-iNSCLC) cases to quantify the density, proportion, and spatial proximity of CD8<sup>+</sup> T cells, M2 macrophages, neutrophils, FOXP3<sup>+</sup> cells, and IFNα<sup>+</sup> cells within the immune landscape, and to assess their associations with treatment efficacy and prognosis.</div></div><div><h3>Results</h3><div>Lower infiltration of CD8<sup>+</sup>T cells and IFNα<sup>+</sup> cells, but higher infiltration of M2 macrophages in the overall immune landscape, was observed in SMARCA4-UT compared with SMARCA4–iNSCLC (<em>P</em> < 0.05). Patients with higher CD8<sup>+</sup>T cells and IFNα<sup>+</sup> cells infiltration had longer overall survival (OS) following immunotherapy. Multivariate Cox regression identified high CD8<sup>+</sup>T cell infiltration as an independent protective prognostic factor in the SMARCA4-UT group (HR = 0.204, <em>P</em> = 0.017). Within the TIME of SMARCA4-UT, CD8<sup>+</sup>T cells, FOXP3<sup>+</sup> cells, and IFNα<sup>+</sup> cells were located in closer proximity to M2 macrophages. The distance between individual M2 macrophages was significantly shorter; conversely, neutrophils were positioned further away from M2 macrophages (<em>P</em> < 0.05). Further, greater distance between M2 macrophages and CD8<sup>+</sup>T cells correlated with better prognosis (HR = 0.834, <em>P</em> = 0.047) and a significantly longer median OS (<em>P</em> = 0.016).</div></div><div><h3>Conclusion</h3><div>The TIME of SMARCA4-UT is characterized by an immune-desert phenotype, and higher CD8<sup>+</sup>T cells infiltration is associated with improved immunotherapeutic efficacy. Spatial proximity between M2 macrophages and multiple immune cell subsets within the TIME of SMARCA4-UT is markedly increased.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108817"},"PeriodicalIF":4.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prognostic value of preoperative ctDNA and pathological venous invasion for recurrence in EGFR-mutated non-small cell lung cancer 术前ctDNA和病理性静脉浸润对egfr突变的非小细胞肺癌复发的预后价值

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-04 DOI: 10.1016/j.lungcan.2025.108818

Yuya Murase , Hayato Koba , Hideharu Kimura , Isao Matsumoto , Tsukasa Ueda , Shunichi Nomura , Sachiko Arai , Nanao Terada , Liu Yifeng , Shigeki Nanjo , Yuichi Tambo , Takafumi Kobayashi , Satoshi Watanabe , Kenta Yamamura , Noriyuki Ohkura , Miki Abo , Akihiro Nomura , Seiji Yano

Introduction

Curative surgery followed by adjuvant osimertinib according to pathological stage (pStage) is standard for resectable epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Nevertheless, recurrence remains a concern even in Stage IA, for which adjuvant osimertinib is not indicated. We evaluated the utility of circulating tumor DNA (ctDNA) to predict recurrence in patients with resected pStage I-III EGFR-mutated NSCLC and examined prognostic value of preoperative biomarkers and pathological features.

Methods

Between January 2017 and May 2020, 382 patients with lung tumors underwent surgery at Kanazawa University Hospital, including 88 with NSCLC harboring common EGFR mutations. Preoperative ctDNA was analyzed using droplet digital PCR, targeting EGFR mutations. Patients were followed for up to 6.4 years, and disease-free survival (DFS) and overall survival (OS) were evaluated.

Results

Preoperative ctDNA positivity was detected in 26.1 % and venous invasion in 39.8 %. ctDNA-positive patients had lower 60-month DFS (54.1 % vs. 84.1 %; HR = 3.25; 95 % CI, 1.13–9.21; p = 0.028) and 60-month OS (65.1 % vs. 95.9 %; HR = 6.10; 95 % CI, 1.11–33.46; p = 0.037). Venous invasion was independently associated with poorer DFS (HR = 8.73; 95 % CI, 1.81–41.93; p = 0.0068). In combined analyses, no recurrences occurred in the double-negative, whereas the double-positive had a lower 60-month DFS than the single-positive (HR = 3.61; 95 % CI, 1.19–10.93; p = 0.023).

Conclusion

Preoperative ctDNA detection and pathological venous invasion provide complementary prognostic information, and venous invasion is an independent predictor of recurrence risk in EGFR-mutated NSCLC. Combined assessment may refine postoperative risk stratification and inform perioperative management.

根据病理分期（pStage）进行根治性手术后辅以奥希替尼是可切除的表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）的标准治疗方法。然而，即使在IA期，复发仍然是一个问题，辅助奥希替尼不适用。我们评估了循环肿瘤DNA （ctDNA）在预测切除的pi - iii期egfr突变的非小细胞肺癌患者复发中的应用，并检查了术前生物标志物和病理特征的预后价值。方法2017年1月至2020年5月，382例肺肿瘤患者在金泽大学医院接受了手术，其中88例患有常见EGFR突变的非小细胞肺癌。术前ctDNA分析采用液滴数字PCR，靶向EGFR突变。患者随访6.4年，评估无病生存期（DFS）和总生存期（OS）。结果术前ctDNA阳性占26.1%，静脉浸润占39.8%。ctdna阳性患者的60个月DFS（54.1%比84.1%;HR = 3.25; 95% CI, 1.13-9.21; p = 0.028）和60个月OS（65.1%比95.9%;HR = 6.10; 95% CI, 1.11-33.46; p = 0.037）较低。静脉侵犯与较差的DFS独立相关（HR = 8.73; 95% CI, 1.81 ~ 41.93; p = 0.0068）。在联合分析中，双阴性患者没有复发，而双阳性患者的60个月DFS低于单阳性患者（HR = 3.61; 95% CI, 1.19-10.93; p = 0.023）。结论术前ctDNA检测和病理性静脉浸润提供了互补的预后信息，静脉浸润是egfr突变NSCLC复发风险的独立预测因子。综合评估可细化术后风险分层，为围手术期管理提供信息。

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引用次数: 0

Factors associated with lung cancer-specific mortality in lung cancer screening programs 肺癌筛查项目中与肺癌特异性死亡率相关的因素

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-03 DOI: 10.1016/j.lungcan.2025.108815

Esther Tannoury, Suzanne C. Byrne, Mark M. Hammer

Objectives

Two major clinical trials have proven lung cancer screening (LCS) to be effective in reducing lung cancer-specific mortality. However, mortality reduction in the trials was only 20%. Our objective is to identify the causes contributing to lung cancer-specific death in our screening population.

Methods

This retrospective study reviewed all patients who were enrolled in our healthcare system’s lung cancer screening program between January 2015 and June 2023. Chart reviews were performed of all patients who died after lung cancer diagnosis to first determine whether the death was attributed to lung cancer. We then performed a chart review to identify contributing factors to death, including: advanced stage at initial diagnosis; non-compliance; missed nodules; aggressive cancers; recurrence; and treatment complications.

Results

During study period, 15,762 patients were screened, 694 were diagnosed with lung cancer, and 112 deaths were attributed directly to lung cancer. Potentially modifiable factors contributing to lung cancer-specific death accounted for the majority of causes (66/112; 59%), with advanced stage at initial diagnosis being the leading factor (28/112; 25%) followed by non-compliance (26/112; 23%) and missed nodules on CT (12/112; 11%). Non-modifiable contributing factors included development of an aggressive lung cancer (16/112; 14%), cancer recurrence after early stage (14/112; 13%), development of a second lung cancer (10/112; 9%), and treatment complications (6/112; 5%).

Conclusion

Potentially modifiable factors contributed to the majority of lung cancer-related deaths in our screening program. Interventions to improve uptake of screening and follow-up may be able to improve the efficacy of lung cancer screening programs.

两项主要的临床试验已经证明肺癌筛查（LCS）在降低肺癌特异性死亡率方面是有效的。然而，试验中的死亡率仅降低了20%。我们的目标是在筛查人群中确定导致肺癌特异性死亡的原因。方法本回顾性研究回顾了2015年1月至2023年6月期间参加我们医疗保健系统肺癌筛查计划的所有患者。对所有肺癌诊断后死亡的患者进行图表回顾，首先确定死亡是否归因于肺癌。然后，我们进行了一次图表回顾，以确定导致死亡的因素，包括：初步诊断时处于晚期；不符合;错过了结节;激进的癌症;复发;治疗并发症。结果在研究期间，15762名患者接受了筛查，694名患者被诊断为肺癌，112名患者直接死于肺癌。导致肺癌特异性死亡的潜在可改变因素占大多数原因（66/112;59%），其中初始诊断晚期是主要因素（28/112;25%），其次是不合规（26/112;23%）和CT未发现结节（12/112;11%）。不可改变的影响因素包括侵袭性肺癌的发展（16/112;14%）、早期癌症复发（14/112;13%）、第二肺癌的发展（10/112;9%）和治疗并发症（6/112;5%）。结论：在我们的筛查项目中，潜在的可改变因素导致了大多数肺癌相关死亡。提高筛查和随访率的干预措施可能会提高肺癌筛查项目的疗效。

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引用次数: 0

A novel agent, p-toluenesulfonamide, in the management of malignant pleural effusions 一种新型药物，对甲苯磺酰胺，在恶性胸腔积液的管理

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-03 DOI: 10.1016/j.lungcan.2025.108814

Yung-Hung Luo , Chuan-Ching Yang , Shun-Chi Wu , Hsiao-Wen Su , Yi-Chin Hsing , Shih-Yuan Lin , Yun-Chi Lo , Mao-Yuan Lin , Shi-yue Li , Jianxing He , Shuenn-Wen Kuo

Background

Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity, with unclear underlying mechanisms and limited effective treatments. Current therapies, such as talc insufflation, effectively achieve pleurodesis but result in irreversible pleural adhesion, significantly impacting patient quality of life. Para-toluenesulfonamide (PTS), a small molecule, has demonstrated anticancer activity in preclinical and clinical studies.

Methods

To evaluate the safety and efficacy of PTS for MPE treatment, we conducted preclinical and clinical exploratory studies.

Results

In a mouse MPE model, intrapleural injection of PTS significantly reduced effusion volume and pleural tumor weight without causing pleural adhesions or loculation. Clinical studies in China and Taiwan further supported these findings. In China, 17 patients treated with intrapleural PTS achieved an MPE response rate of 76.5 % at treatment completion and 41.2 % maintained control at four weeks post-treatment. Quality of life, assessed by FACT-L scores, improved significantly without serious adverse events. In Taiwan, seven lung cancer patients treated with intrapleural PTS showed significant reduction in drained effusion volume from baseline to 30 days post-treatment. The MPE response rate was 85.7 %, with a disease control rate of 100 %. The median time to reintervention was 84 days, with no observed pleural adhesions or serious adverse effects.

Conclusion

Collectively, these results indicate that PTS effectively inhibits tumor growth, reduces MPE accumulation, and avoids pleural adhesion, highlighting its potential as a promising therapeutic option for managing MPE. Further comprehensive studies are warranted to establish its clinical role.

恶性胸腔积液（MPE）是各种人类癌症转移到胸腔的致命后果，其潜在机制尚不清楚，有效治疗方法有限。目前的治疗方法，如滑石粉注入，可以有效地实现胸膜切除术，但会导致不可逆的胸膜粘连，严重影响患者的生活质量。对甲苯磺酰胺（PTS）是一种小分子物质，在临床前和临床研究中显示出抗癌活性。方法为了评价PTS治疗MPE的安全性和有效性，我们进行了临床前和临床探索性研究。结果在小鼠MPE模型中，胸膜内注射PTS可显著减少胸腔积液量和胸膜肿瘤重量，且不引起胸膜粘连和定位。中国大陆和台湾的临床研究进一步支持了这些发现。在中国，17名接受胸膜内PTS治疗的患者在治疗完成时的MPE缓解率为76.5%，治疗后4周时的MPE缓解率为41.2%。以FACT-L评分评估的生活质量显著改善，无严重不良事件发生。在台湾，7名接受胸膜内PTS治疗的肺癌患者在治疗后30天，排出的积液量从基线到治疗后30天显著减少。MPE有效率为85.7%，疾病控制率为100%。再干预的中位时间为84天，未观察到胸膜粘连或严重不良反应。总之，这些结果表明PTS有效抑制肿瘤生长，减少MPE积累，避免胸膜粘连，突出了其作为治疗MPE的有前途的治疗选择的潜力。需要进一步的综合研究来确定其临床作用。

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引用次数: 0

Clinical characteristics and outcomes in participants with screen-detected clinical stage I lung cancer in the Yorkshire lung screening trial: A comparison of surgery versus stereotactic ablative radiotherapy 在约克郡肺筛查试验中筛查到临床I期肺癌的临床特征和结果：手术与立体定向消融放疗的比较

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-03 DOI: 10.1016/j.lungcan.2025.108816

Hannah R. Bailey , Hui Zhen Tam , Daniel Vulkan , Alessandro Brunelli , Philip A.J. Crosbie , Kevin N. Franks , Rhian Gabe , Martyn P.T. Kennedy , Matthew E.J. Callister

Background

Lung cancer screening with low-dose computed tomography (LDCT) saves lives by detecting early-stage curable cancer and estimates of overdiagnosis in the previous randomised studies were generally low. Screening selection criteria vary, with some programmes only recommending screening for people who are surgical candidates, whereas others make no reference to fitness for surgery. Here we report clinical characteristics and outcomes for participants in the Yorkshire Lung Screening Trial with screen-detected clinical stage I lung cancer according to treatment modality.

Methods

Consecutive participants with screen-detected clinical stage I lung cancer were stratified according to curative treatment modality into surgical and SABR cohorts. Factors associated with overall survival and cancer-specific survival were assessed with a median follow-up of 3.6 years.

Results

Of 190 patients with stage I lung cancer studied, 31 % (n = 58) received SABR and 69 % (n = 132) surgery (55 lobectomy, 77 sub-lobar resection). Patients treated with SABR were older with worse performance status and fitness parameters. Cancer-specific survival was similar between the SABR and surgery cohorts (HR for death 1.19, 95 % CI 0.45–3.14, p = 0.72) but overall survival was worse following SABR compared to surgery (HR for death 2.61 95 % CI 1.45–4.69, p = 0.001), indicating that the worse overall survival was due to non-cancer deaths. In the SABR cohort 17 patients (29.3 %) died from non-cancer causes during the study follow-up period compared with 9 (6.8 %) in the surgery cohort. Three-year survival was 69.4 % in the SABR cohort and 92.4 % in the surgical cohort (p < 0.001).

Conclusions

Cancer-specific survival was similar between the two groups, but overall survival following SABR for screen-detected stage I lung cancer is worse than surgery due to higher rates of non-cancer death within 5 years of treatment. Lung cancer sojourn time has been estimated at around 5 years, so it is likely that rates of overdiagnosis are higher in patients treated with SABR compared to surgery. Further research may be needed to optimise inclusion and exclusion criteria for lung cancer screening.

背景：肺癌筛查低剂量计算机断层扫描（LDCT）通过发现早期可治愈的癌症来挽救生命，并且在之前的随机研究中，过度诊断的估计通常很低。筛查选择标准各不相同，有些方案只建议对手术候选者进行筛查，而另一些方案则不考虑是否适合手术。在这里，我们根据治疗方式报告了约克郡肺筛查试验中筛查到临床I期肺癌的参与者的临床特征和结果。方法：连续筛检临床I期肺癌患者按治愈治疗方式分为手术组和SABR组。评估与总生存率和癌症特异性生存率相关的因素，中位随访时间为3.6年。结果：在研究的190例I期肺癌患者中，31% （n = 58）接受了SABR， 69% （n = 132）接受了手术（肺叶切除术55例，叶下切除术77例）。接受SABR治疗的患者年龄较大，运动状态和体能参数较差。SABR组和手术组的癌症特异性生存率相似（死亡风险比为1.19,95% CI 0.45-3.14, p = 0.72），但SABR组的总生存率比手术组差（死亡风险比为2.61,95% CI 1.45-4.69, p = 0.001），表明较差的总生存率是由于非癌症死亡。在SABR队列中，17例（29.3%）患者在研究随访期间死于非癌症原因，而手术队列中为9例（6.8%）。SABR组的3年生存率为69.4%，手术组的3年生存率为92.4% (p结论：两组的癌症特异性生存率相似，但筛查检测到的I期肺癌SABR后的总体生存率低于手术，因为治疗5年内非癌症死亡率更高。肺癌停留时间估计约为5年，因此与手术相比，SABR患者的过度诊断率可能更高。可能需要进一步的研究来优化肺癌筛查的纳入和排除标准。

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引用次数: 0

Recommendations for radiotherapy in patients with lung cancer and interstitial lung disease: A Delphi consensus process of the Italian association of radiotherapy and clinical oncology (AIRO) 肺癌和间质性肺疾病患者的放疗建议：意大利放疗和临床肿瘤学协会（AIRO）的德尔菲共识过程。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-03 DOI: 10.1016/j.lungcan.2025.108807

Paolo Borghetti , Rolando D’Angelillo , Giorgio Facheris , Andrea Borghesi , Alessio Bruni , Paolo Ceruti , Katia Ferrari , Andrea Riccardo Filippi , Sara Ramella , Diego Signorelli , Giovanni Pappagallo , Umberto Ricardi

Aim

Interstitial lung diseases (ILD) are a group of disorders affecting the lung parenchyma. ILD patients have a higher risk of lung cancer and worse prognosis, with increased susceptibility to radiotherapy (RT)-related toxicities due to ILD exacerbations. There are no clear guidelines for managing lung cancer patients with ILD undergoing RT, alone or with systemic therapies. This work aims to establish a consensus on ILD assessment, patient selection, risk/benefit analysis, and clinical management for those eligible for thoracic RT.

Methods

Using the Estimate-Talk-Estimate method, a board of experts (4 radiation oncologists, 2 pneumologists, 1 radiologist, 1 medical oncologist) identified key items. Each expert drafted statements for these items, and an extended panel of 24 experts (12 radiation oncologists, 6 pneumologists, 3 radiologists, 3 medical oncologists) rated the statements on a 9-point scale. Consensus was defined as a median score ≥ 7.

Results

Sixteen statements from 10 items reached consensus. The consensus points reached concern the clinical, radiological and functional assesment of patients with ILD, the role of the multidisciplinary team, the accurate evaluation of toxicity predictors, the prevention of complications and the risk/benefit ratio in different clinical scenarios in which radiotherapy is administered alone or in combination with antineoplastic drugs. Conclusion This multidisciplinary consensus on thoracic RT for lung cancer patients with ILD provides valuable guidance for clinicians managing this complex scenario.

目的：间质性肺疾病（ILD）是一类影响肺实质的疾病。ILD患者有较高的肺癌风险和较差的预后，由于ILD恶化，对放疗（RT）相关毒性的易感性增加。目前还没有明确的指导方针来管理肺癌ILD患者接受放疗，单独或全身治疗。本研究旨在就ILD评估、患者选择、风险/收益分析和符合胸段放疗条件的患者临床管理建立共识。方法：由专家委员会（4名放射肿瘤学家、2名肺部肿瘤学家、1名放射学家、1名内科肿瘤学家）采用Estimate-Talk-Estimate方法确定关键项目。每位专家为这些项目起草声明，由24名专家组成的扩展小组（12名放射肿瘤学家、6名肺病学家、3名放射科医生、3名医学肿瘤学家）以9分制对声明进行评分。共识定义为中位数得分≥7。结果：10项16项表述达成共识。达成的共识涉及ILD患者的临床、放射学和功能评估、多学科团队的作用、毒性预测因子的准确评估、并发症的预防以及在单独放疗或与抗肿瘤药物联合放疗的不同临床情况下的风险/收益比。结论：多学科对肺癌合并ILD患者胸部放疗的共识为临床医生处理这一复杂情况提供了有价值的指导。

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引用次数: 0

First-line immunotherapy ± chemotherapy with or without upfront stereotactic radiotherapy (SRT) in patients with Non-Small cell lung cancer (NSCLC) with asymptomatic brain metastases 非小细胞肺癌（NSCLC）无症状脑转移患者的一线免疫治疗±化疗伴或不伴前期立体定向放疗（SRT）

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-11-03 DOI: 10.1016/j.lungcan.2025.108813

Lorenz Frehner , Sämi Schär , Stefanie Hayoz , Verena Petermichl , Philip Speicher , Sacha I. Rothschild , Laetitia A. Mauti , David König , Tobias Finazzi , Patrizia Froesch , Sabrina Marini , Anna Allemann , Michael Mark , Wolf-Dieter Janthur , Antonia Stamatiou , Yannis Metaxas , Ekin Ermiş , Franca Wagner , Martin Früh , Sabine Schmid

Background

The role and optimal timing of SRT for patients with advanced NSCLC and asymptomatic brain metastases treated with immune checkpoint inhibitors (ICI) are controversial.

Methods

Efficacy and safety outcomes of patients with newly diagnosed non oncogene- addicted NSCLC with asymptomatic brain metastases (1–10 lesions, max. diameter of lesions 3 cm) treated with a first-line ICI-containing regimen at 11 Swiss cancer centers were retrospectively analyzed.

Results

A total of 128 patients in two cohorts (58 patients with upfront SRT and 69 patients without upfront SRT) were included in this analysis. The median intracranial progression-free survival (PFS) was significantly longer in patients with upfront SRT (12.6 vs. 8.2 months, Hazard ratio (HR) 0.62 [95 % CI 0.41 vs. 0.95], p = 0.026). This benefit remained significant after correcting for number and size of lesions and programmed cell death 1 ligand (PD-L1) status. The proportion of patients with symptomatic progression of brain metastases and of patients receiving further local treatment to the brain was similar between cohorts (3 % vs. 12 %, p = 0.11 and 33 % vs. 42 %, p = 0.3). No significant difference in median overall survival (OS) was observed between the cohorts (22.8 vs. 21.7 months, p = 0.4). Only two patients with upfront SRT experienced a clinically significant Central Nervous System (CNS) adverse event (AE).

Conclusion

In this multicentric retrospective analysis of patients with asymptomatic brain metastases upfront SRT was associated with an improved intracranial PFS and was well tolerated but median OS and the rate of patients developing symptomatic brain progression were similar to patients without upfront SRT.

背景：对于接受免疫检查点抑制剂（ICI）治疗的晚期非小细胞肺癌和无症状脑转移患者，SRT的作用和最佳时机存在争议。方法：新诊断的非癌基因成瘾非小细胞肺癌伴无症状脑转移（1-10个病灶，最大10个）患者的疗效和安全性结局。回顾性分析了11个瑞士癌症中心采用一线含ici方案治疗的病变直径（3cm）。结果：两组共128例患者（58例接受前期SRT治疗和69例未接受前期SRT治疗）被纳入本分析。术前SRT患者的中位颅内无进展生存期（PFS）明显更长（12.6个月vs. 8.2个月，风险比（HR） 0.62 [95% CI 0.41 vs. 0.95], p = 0.026）。在校正病变的数量和大小以及程序性细胞死亡1配体（PD-L1）状态后，这种益处仍然显著。脑转移症状进展的患者比例和接受进一步局部脑治疗的患者比例在队列之间相似（3%对12%，p = 0.11, 33%对42%，p = 0.3）。两组患者的中位总生存期（OS）无显著差异（22.8个月vs. 21.7个月，p = 0.4）。只有两名患者经历了临床显著的中枢神经系统不良事件（AE）。结论：在这项无症状脑转移患者的多中心回顾性分析中，前期SRT与颅内PFS改善相关，耐受性良好，但中位OS和出现症状性脑进展的患者率与未进行前期SRT的患者相似。

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引用次数: 0