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Clinical benefit evaluation of drug treatment regimens for advanced lung cancer:based on ASCO-VF and ESMO-MCBS 晚期肺癌药物治疗方案的临床效益评估:基于 ASCO-VF 和 ESMO-MCBS。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.lungcan.2024.108001
Jingdan Pang , Yiruo Zhang , Xuan Wang , Wentian Wu , Chang Wan , Ziming Li , Yingying Du

Background

With the increasing use of novel targeted drugs and immune checkpoint inhibitors (ICIs) for lung cancer (LC), the life expectancy of patients with LC has notably increased. In China, many drugs with the same mechanism of action have been approved by the National Medical Products Administration (NMPA) through phase III randomized controlled trials (RCTs). However, differences occur in these drugs’ efficacy and adverse effects, all of which have been compared with standard treatments, and data from head-to-head studies are lacking.

Methods

The key RCTs of EGFR tyrosine kinase inhibitors (EGFR-TKIs), ALK-TKIs, and ICIs approved by NMPA in advanced LC in China were searched and divided into five groups. The American Society of Clinical Oncology Value Framework (ASCO-VF v2) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS v1.1) were used to evaluate the net health benefits (NHB) of RCTs, including efficacy, adverse reactions, and patient-reported outcomes (PROs), etc. The consistency of the ASCO-VF and ESMO-MCBS was compared.

Results

As of September 2024, 37 RCTs have been included in the ASCO-VF and ESMO-MCBS. NHB scores ranged from 12.30 to 93.25. Nineteen trials met the ASCO-VF “substantial benefit”, and 28 trials achieved the ESMO-MCBS “substantial benefit”. Except for icotinib, dacomitinib, and befotertinib, all EGFR-TKIs and ALK-TKIs met the threshold of two frameworks. In the ICI regimens, eight regimens met the threshold of “ substantial benefit ” as defined by the two frameworks and nine studies showed conflicting results. The correlation coefficient of the 37 pairs of scores in the advanced LC study was estimated to be 0.473(Spearman), and the consistency analysis showed fair agreement.(κ = 0.265, p = 0.001).

Conclusions

ASCO-VF and ESMO-MCBS focus on clinical efficacy and consider the adverse effects of drugs and PROs. We look forward to head-to-head studies on the different treatment options and advocate refining the ESMO-MCBS.
背景:随着新型靶向药物和免疫检查点抑制剂(ICIs)越来越多地用于肺癌治疗,肺癌患者的预期寿命显著延长。在中国,许多具有相同作用机制的药物已通过 III 期随机对照试验(RCT)获得国家医药产品管理局(NMPA)批准。然而,这些药物在疗效和不良反应方面存在差异,且均与标准疗法进行过比较,缺乏头对头研究的数据:方法:检索了经NMPA批准的中国晚期LC的表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)、ALK-TKIs和ICIs的主要RCT,并将其分为五组。采用美国临床肿瘤学会价值框架(ASCO-VF v2)和欧洲肿瘤内科学会临床获益量表(ESMO-MCBS v1.1)评价RCT的净健康获益(NHB),包括疗效、不良反应和患者报告结局(PROs)等。比较了 ASCO-VF 和 ESMO-MCBS 的一致性:结果:截至 2024 年 9 月,ASCO-VF 和 ESMO-MCBS 共纳入了 37 项 RCT。NHB评分从12.30分到93.25分不等。19项试验达到了ASCO-VF的 "实质性获益 "标准,28项试验达到了ESMO-MCBS的 "实质性获益 "标准。除了icotinib、dacomitinib和befotertinib外,所有EGFR-TKIs和ALK-TKIs都达到了两个框架的阈值。在 ICI 方案中,有 8 项方案达到了两个框架所定义的 "实质性获益 "阈值,有 9 项研究显示了相互矛盾的结果。晚期LC研究中37对评分的相关系数估计为0.473(Spearman),一致性分析表明一致性尚可(κ = 0.265, p = 0.001):ASCO-VF和ESMO-MCBS关注临床疗效,并考虑了药物的不良反应和PROs。我们期待对不同的治疗方案进行头对头研究,并主张完善ESMO-MCBS。
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引用次数: 0
Corrigendum to “Real-world treatment sequencing and effectiveness of second- and third-generation ALK tyrosine kinase inhibitors for ALK -positive advanced non-small cell lung cancer” [Lung Cancer 195 (2024) 107919] 第二代和第三代 ALK 酪氨酸激酶抑制剂治疗 ALK 阳性晚期非小细胞肺癌的真实世界治疗排序和有效性"[Lung Cancer 195 (2024) 107919]的更正。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.lungcan.2024.108000
Jessica R. Bauman , Geoffrey Liu , Isabel Preeshagul , Stephen V. Liu , Barbara Melosky , Devin Abrahami , Benjamin Li , Despina Thomaidou , Kirsten Duncan , Stan Krulewicz , Martin Rupp , Jessica J. Lin
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引用次数: 0
Real-world comparison of the efficacy and safety of atezolizumab versus durvalumab in extensive-stage small cell lung cancer 阿特珠单抗与度伐单抗在广泛期小细胞肺癌中的疗效和安全性的真实世界比较
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.lungcan.2024.107999
Megan Vince , Syeda Mahrukh Hussnain Naqvi , Bruna Pellini , Michael Verbosky , Dan Melzer

Background

Small cell lung cancer (SCLC) is an aggressive disease associated with high relapse rates and limited treatment options. Current standard of care treatment for extensive-stage disease includes combination chemotherapy plus immunotherapy. Programmed death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are preferred first-line treatments in combination with chemotherapy with both atezolizumab and durvalumab being equivalent options. Although both ICIs are listed as front-line options in clinical guidelines, there have been no head-to-head trials comparing durvalumab to atezolizumab. Therefore, it is unknown if either agent is superior with regards to efficacy or safety.

Methods

This retrospective, single-institution study examined patients with extensive-stage small cell lung cancer presenting to Moffitt Cancer Center between October 1st, 2018 to May 31st, 2023 who received either atezolizumab or durvalumab in combination with a platinum-doublet in the first-line setting. To be included in this analysis patients must have received at least two cycles of induction chemotherapy and ICI and one cycle of maintenance ICI. The primary outcome of this study was overall survival. The secondary outcomes include progression-free survival, immune-related adverse events, hospitalizations due to ICIs, and progression-free survival on second-line therapy (PFS2).

Results

Of the 101 patients included, 55 received durvalumab (54.5 %) and 46 received atezolizumab (45.5 %). The median overall survival in the durvalumab and atezolizumab arms were 14.7 versus 11.6 months, respectively (HR 0.59; 95 % CI, 0.38–0.92; P = 0.020). There was not a statistically significant difference in median progression-free survival between the two arms (6.3 versus 5.9 months, P = 0.344). Atezolizumab was associated with a numerically higher incidence of immune-related adverse events (47.8 % versus 32.7 %, P = 0.157) and hospitalization rates for those with an immune-related adverse event (36.4 % versus 16.7 %, P = 0.204). PFS2 was 2.3 months in the atezolizumab arm and 3.4 months in the durvalumab arm (HR 1.24; 95 % CI, 0.69–2.23; P = 0.466).

Conclusions

In this real-world retrospective study, durvalumab was associated with improved overall survival in patients with extensive-stage small cell lung cancer consistent with previous findings from a similar study in a Chinese patient population. Although not statistically significant, there was a lower incidence of immune-related adverse events in the durvalumab arm as well as ICI-related hospitalizations. PFS2 was not statistically significant different between arms.
背景小细胞肺癌(SCLC)是一种侵袭性疾病,复发率高,治疗方案有限。目前治疗广泛期疾病的标准疗法包括联合化疗加免疫疗法。程序性死亡配体-1(PD-L1)免疫检查点抑制剂(ICIs)是联合化疗的首选一线治疗药物,atezolizumab和durvalumab是同等的选择。虽然这两种 ICIs 都被列为临床指南中的一线选择,但目前还没有头对头试验对 durvalumab 和 atezolizumab 进行比较。因此,这两种药物在疗效或安全性方面是否更胜一筹尚不得而知。方法这项回顾性、单一机构研究考察了2018年10月1日至2023年5月31日期间在莫菲特癌症中心就诊的广泛期小细胞肺癌患者,这些患者在一线治疗中接受了阿特珠单抗或durvalumab联合铂类双药治疗。患者必须接受过至少两个周期的诱导化疗和 ICI 以及一个周期的维持 ICI 治疗,才能纳入本分析。本研究的主要结果是总生存期。次要结果包括无进展生存期、免疫相关不良事件、因 ICIs 导致的住院治疗以及二线治疗的无进展生存期(PFS2)。结果 在纳入的 101 例患者中,55 例接受了 durvalumab(54.5%),46 例接受了 atezolizumab(45.5%)。达伐单抗和阿特珠单抗治疗组的中位总生存期分别为14.7个月和11.6个月(HR 0.59; 95 % CI, 0.38-0.92; P = 0.020)。两组患者的中位无进展生存期差异无统计学意义(6.3 个月对 5.9 个月,P = 0.344)。阿特珠单抗与较高的免疫相关不良事件发生率(47.8% 对 32.7%,P = 0.157)和免疫相关不良事件患者的住院率(36.4% 对 16.7%,P = 0.204)相关。结论在这项真实世界回顾性研究中,阿特珠单抗治疗组的总生存期为2.3个月,而杜瓦单抗治疗组为3.4个月(HR 1.24; 95 % CI, 0.69-2.23; P = 0.466)。尽管没有统计学意义,但在杜瓦鲁单抗治疗组中,免疫相关不良事件的发生率以及ICI相关住院率均较低。两组间的PFS2差异无统计学意义。
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引用次数: 0
The relevance of the reference range for EGFR testing in non-small cell lung cancer patients 非小细胞肺癌患者表皮生长因子受体检测参考范围的相关性
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.lungcan.2024.108002
Pasquale Pisapia , Alessandro Russo , Caterina De Luca , Francesco Pepe , Francesco Drago , Christian Rolfo , Giancarlo Troncone , Umberto Malapelle

Introduction

Identifying mutations in the epidermal growth factor receptor (EGFR) gene is crucial for individualized treatment of non-small cell lung cancer (NSCLC) patients. Accordingly, several methodologies and instruments are now commercially available to detect these alterations. The aim of this study was to examine the performance of next generation sequencing (NGS) in detecting both common and uncommon EGFR gene mutations in advanced NSCLC patients.

Methods

We retrospectively retrieved molecular data from n = 1312 advanced stage NSCLC patients tested by our NGS DNA-based panel (namely SiRe® panel) from January 2018 to December 2022. We subsequently compared the NGS results with the reference ranges of the most popular real time PCR (RT-qPCR) assays (cobas® EGFR Mutation Test v2, EasyPGX® ready EGFR, Idylla™ EGFR mutation test, and therascreen® EGFR Plus RGQ).

Results

Overall, NGS detected n = 234 mutations in n = 192 (15.9 %) patients. Conversely, when these results were compared with the reference ranges of the four most common commercially available RT-qPCR assays, far fewer mutations were identified: n = 18 (9.4 %), n = 17 (8.9 %), n = 17 (8.9 %), and n = 18 (9.4 %) mutations. These results suggest that if patients were tested solely using RT-qPCR assays, a substantial proportion would have been ineligible for targeted therapies.

Conclusions

Our study highlights that NGS is able to identify a much higher number of actionable EGFR mutations than RT-qPCR approaches, thereby providing many more patients the opportunity to receive targeted EGFR treatments.
导言确定表皮生长因子受体(EGFR)基因的突变对于非小细胞肺癌(NSCLC)患者的个体化治疗至关重要。因此,目前市场上有多种方法和仪器可用于检测这些基因突变。本研究旨在检测新一代测序(NGS)在检测晚期 NSCLC 患者常见和不常见表皮生长因子受体基因突变方面的性能。方法我们回顾性地检索了 2018 年 1 月至 2022 年 12 月期间通过我们基于 NGS DNA 的面板(即 SiRe® 面板)检测的 n = 1312 例晚期 NSCLC 患者的分子数据。随后,我们将 NGS 结果与最流行的实时 PCR (RT-qPCR) 检测方法(cobas® EGFR 突变检测 v2、EasyPGX® ready EGFR、Idylla™ EGFR 突变检测和 therascreen® EGFR Plus RGQ)的参考范围进行了比较。结果总体而言,NGS 在 n = 192(15.9%)名患者中检测到 n = 234 个突变。相反,当这些结果与四种最常见的市售 RT-qPCR 检测方法的参考范围进行比较时,发现的突变少得多:n = 18(9.4%)、n = 17(8.9%)、n = 17(8.9%)和 n = 18(9.4%)个突变。这些结果表明,如果仅使用 RT-qPCR 检测方法对患者进行检测,很大一部分患者将不符合接受靶向治疗的条件。结论我们的研究强调,与 RT-qPCR 方法相比,NGS 能够鉴定出更多可操作的表皮生长因子受体突变,从而为更多患者提供接受表皮生长因子受体靶向治疗的机会。
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引用次数: 0
Putative mechanisms of primary resistance to EGFR-targeted therapies: A retrospective study 表皮生长因子受体靶向疗法原发性耐药的可能机制:回顾性研究
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.lungcan.2024.107998
Xueliang Tu , Zhongyu Lu , Fengrong Hei , Tong Zhang , Xiaoxuan Wang , Dongsheng Chen , Fengjuan Fan , Jing Xu , Xing Zhang , Kefeng Guo

Backgrounds

Advanced lung adenocarcinoma (LUAD) patient with EGFR mutations often experience resistance to first-line epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) therapy. Nonetheless, the mechanism and biomarkers of primary resistance remain unclear. Further exploration of independent prognostic factors will help clinicians identify patients who may not respond to EGFR-TKIs and select appropriate treatment strategies.

Methods

A retrospective study involving 124 patients with stage IV LUAD harboring a common sensitizing EGFR mutation (exon 19 deletion or L858R mutation) who received EGFR-TKIs as first-line therapy was performed. All participants were tested by DNA-targeted sequencing in baseline samples, and there were 19 patients with progression-free survival (PFS) ≤ 3 months (cohort 1, C1, primary resistance), 22 patients with 3 < PFS < 8 months (cohort 2, C2, poor response) without known mutations associated with resistance, and 83 patients with PFS ≥ 8 months (cohort 3, C3, normal).

Results

The most commonly mutated genes at baseline in patients prior to treatment within the entire study population. were TP53 (65 %), MYC (19 %), CDKN2A (12 %), MUC16 (12 %) and RBM10 (12 %). The baseline characteristics, except for the proportions of patients with EGFR L858R mutation and exon 19 deletion in C1 plus C2 compared to C3 (p = 0.036), were not significantly different among the cohorts. The frequencies of PIK3C2G, STK11, EPAS1, RARA and BTG2 variation were significantly higher in C1, the primary resistance group. Multivariate Cox analysis revealed that PIK3C2G (HR 15.70 95 % CI 3.24–76.05, p < 0.001), STK11 (HR 17.04, 95 % CI 3.68–78.92, p < 0.001), EPAS1 (HR 11.99, 95 % CI 2.57–56.03, p = 0.002), and BTG2 amplification (HR 9.53, 95 % CI 1.67–54.28, p = 0.011) were significantly associated with shorter PFS.

Conclusions

The genomic landscape varies significantly among patients with LUAD, which should be considered when making personalized treatment decisions. This information could provide insights into molecular changes and their effects on clinical treatment in diverse patients with LUAD harboring sensitizing EGFR mutations.
背景表皮生长因子受体(EGFR)突变的晚期肺腺癌(LUAD)患者通常会对一线表皮生长因子酪氨酸激酶抑制剂(EGFR-TKIs)治疗产生耐药性。然而,原发性耐药的机制和生物标志物仍不清楚。该研究涉及124名携带常见致敏表皮生长因子受体突变(19外显子缺失或L858R突变)并接受EGFR-TKIs一线治疗的IV期LUAD患者。所有参与者都接受了基线样本的DNA靶向测序检测,其中19名患者的无进展生存期(PFS)≤3个月(队列1,C1,原发性耐药),22名患者的无进展生存期(PFS)≤3个月(队列2,C2,不良反应),83名患者的无进展生存期(PFS)≥8个月(队列3,C3,正常)。结果在整个研究人群中,治疗前患者基线最常见的突变基因是TP53(65%)、MYC(19%)、CDKN2A(12%)、MUC16(12%)和RBM10(12%)。除了C1和C2中表皮生长因子受体(EGFR)L858R突变和19号外显子缺失的患者比例高于C3(P = 0.036)外,各组间的基线特征无显著差异。C1是主要耐药组,其PIK3C2G、STK11、EPAS1、RARA和BTG2变异频率明显较高。多变量 Cox 分析显示,PIK3C2G(HR 15.70,95 % CI 3.24-76.05,p <0.001)、STK11(HR 17.04,95 % CI 3.68-78.92,p <0.001)、EPAS1(HR 11.99,95 % CI 2.57-56.03,p = 0.002)和 BTG2 扩增(HR 9.53,95 % CI 1.67-54.28,p = 0.011)与较短的 PFS 显著相关。这些信息有助于深入了解携带表皮生长因子受体突变的不同 LUAD 患者的分子变化及其对临床治疗的影响。
{"title":"Putative mechanisms of primary resistance to EGFR-targeted therapies: A retrospective study","authors":"Xueliang Tu ,&nbsp;Zhongyu Lu ,&nbsp;Fengrong Hei ,&nbsp;Tong Zhang ,&nbsp;Xiaoxuan Wang ,&nbsp;Dongsheng Chen ,&nbsp;Fengjuan Fan ,&nbsp;Jing Xu ,&nbsp;Xing Zhang ,&nbsp;Kefeng Guo","doi":"10.1016/j.lungcan.2024.107998","DOIUrl":"10.1016/j.lungcan.2024.107998","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Advanced lung adenocarcinoma (LUAD) patient with <em>EGFR</em> mutations often experience resistance to first-line epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) therapy. Nonetheless, the mechanism and biomarkers of primary resistance remain unclear. Further exploration of independent prognostic factors will help clinicians identify patients who may not respond to EGFR-TKIs and select appropriate treatment strategies.</div></div><div><h3>Methods</h3><div>A retrospective study involving 124 patients with stage IV LUAD harboring a common sensitizing <em>EGFR</em> mutation (exon 19 deletion or L858R mutation) who received EGFR-TKIs as first-line therapy was performed. All participants were tested by DNA-targeted sequencing in baseline samples, and there were 19 patients with progression-free survival (PFS) ≤ 3 months (cohort 1, C1, primary resistance), 22 patients with 3 &lt; PFS &lt; 8 months (cohort 2, C2, poor response) without known mutations associated with resistance, and 83 patients with PFS ≥ 8 months (cohort 3, C3, normal).</div></div><div><h3>Results</h3><div>The most commonly mutated genes at baseline in patients prior to treatment within the entire study population. were <em>TP53</em> (65 %), <em>MYC</em> (19 %), <em>CDKN2A</em> (12 %), <em>MUC16</em> (12 %) and <em>RBM10</em> (12 %). The baseline characteristics, except for the proportions of patients with <em>EGFR</em> L858R mutation and exon 19 deletion in C1 plus C2 compared to C3 (<em>p</em> = 0.036), were not significantly different among the cohorts. The frequencies of <em>PIK3C2G</em>, <em>STK11</em>, <em>EPAS1</em>, <em>RARA</em> and <em>BTG2</em> variation were significantly higher in C1, the primary resistance group. Multivariate Cox analysis revealed that <em>PIK3C2G</em> (HR 15.70 95 % CI 3.24–76.05, <em>p</em> &lt; 0.001), <em>STK11</em> (HR 17.04, 95 % CI 3.68–78.92, <em>p</em> &lt; 0.001), <em>EPAS1</em> (HR 11.99, 95 % CI 2.57–56.03, <em>p</em> = 0.002), and <em>BTG2</em> amplification (HR 9.53, 95 % CI 1.67–54.28, <em>p</em> = 0.011) were significantly associated with shorter PFS.</div></div><div><h3>Conclusions</h3><div>The genomic landscape varies significantly among patients with LUAD, which should be considered when making personalized treatment decisions. This information could provide insights into molecular changes and their effects on clinical treatment in diverse patients with LUAD harboring sensitizing <em>EGFR</em> mutations.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107998"},"PeriodicalIF":4.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142529138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neoadjuvant therapy in early-stage non-small cell lung cancer: A real-world analysis 早期非小细胞肺癌的新辅助治疗:真实世界分析。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.lungcan.2024.107997
Leyla Ay , Daniel Steiner , Hannah Fabikan , Oliver Illini , Dagmar Krenbek , Thomas Klikovits , Michal Benej , Klaus Kirchbacher , Stefan Watzka , Arschang Valipour , Maximilian Hochmair

Background

Phase 3 trials of neoadjuvant immunotherapy-based regimens have shown promising outcomes in patients with resectable non-small cell lung cancer (NSCLC). However, real-world data on treatment regimens with combined chemoimmunotherapy, patient profiles, and clinical outcomes in those patients are limited.

Methods

This dual-center registry-based study describes clinical patterns and outcomes of using neoadjuvant platinum-based chemoimmunotherapy in patients with resectable NSCLC. The main objective was to evaluate the proportion of patients receiving local therapy after chemoimmunotherapy. Further objectives include pathological outcome, disease-free survival (DFS), and overall survival (OS). Histological samples underwent next-generation sequencing (NGS).

Results

Seventy-two patients (median age 64.5 years (interquartile range (IQR), 59–69); 40.3 % women) were included. Prior to initiation of therapy, NGS was available in 90.3 %. Median follow-up time from date of diagnosis was 374 days (IQR, 241–605). After neoadjuvant therapy, 46 patients underwent surgery and 23 radiotherapy, resulting in 69 patients receiving local therapy. Out of 46 patients who underwent surgery, 22 had pathological complete remission (PR), 11 major PR, and 12 minor PR.
DFS (95 % confidence interval (CI)) in 43 (out of 46) surgical patients with R0 resection was 98 % (93–100), 98 % (93–100) and 81 % (57–100) after 180, 360 and 720 days, respectively. OS (95 % CI) was 97 % (94–100), 90 % (82–99) and 90 % (82–99), after 180, 360 and 720 days, respectively.

Conclusion

Following neoadjuvant chemoimmunotherapy, the majority of resectable early-stage NSCLC patients could undergo local therapy in routine clinical practice. This was associated with favorable DFS and OS.
背景:基于新辅助免疫治疗方案的3期试验显示,可切除的非小细胞肺癌(NSCLC)患者的治疗效果很好。然而,有关联合化疗免疫疗法的治疗方案、患者情况和临床疗效的真实世界数据却很有限:这项以双中心登记为基础的研究描述了可切除NSCLC患者使用以铂类为基础的新辅助化疗免疫疗法的临床模式和疗效。主要目的是评估化疗免疫疗法后接受局部治疗的患者比例。其他目标包括病理结果、无病生存期(DFS)和总生存期(OS)。组织学样本进行了新一代测序(NGS):共纳入72名患者(中位年龄为64.5岁(四分位距(IQR)为59-69岁);40.3%为女性)。在开始治疗前,90.3%的患者可获得 NGS。自诊断之日起的中位随访时间为 374 天(IQR,241-605)。新辅助治疗后,46 名患者接受了手术,23 名患者接受了放疗,69 名患者接受了局部治疗。在接受手术的 46 例患者中,22 例病理完全缓解(PR),11 例大缓解,12 例小缓解。43例(共46例)R0切除的手术患者在180天、360天和720天后的DFS(95%置信区间(CI))分别为98%(93-100)、98%(93-100)和81%(57-100)。180 天、360 天和 720 天后的 OS(95 % CI)分别为 97 %(94-100)、90 %(82-99)和 90 %(82-99):新辅助化疗免疫疗法后,大多数可切除的早期NSCLC患者可在常规临床实践中接受局部治疗。结论:新辅助化疗免疫疗法后,大多数可切除的早期NSCLC患者可在常规临床实践中接受局部治疗,这与良好的DFS和OS相关。
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引用次数: 0
Treatment with trimetazidine dihydrochloride and lung cancer survival: Implications on metabolic re-programming 盐酸曲美他嗪治疗与肺癌生存:对代谢重编程的影响
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.lungcan.2024.107996
Yap-Hang Chan , Cheng Yuen-Ting , Chun-Fung Sin , Edmond S.K. Ma , Stephen T.S. Lam , Shiu-Lun Au Yeung , Bernard M.Y. Cheung , Chung-Man Ho , Kai-Hang Yiu , Hung-Fat Tse

Background

Metabolic re-wiring with preferential fatty acid oxidation has been observed in lung cancer cells. Whether the use of trimetazidine, an anti-anginal agent that inhibits fatty acid oxidation, alters clinical outcomes in ischemic heart disease (IHD) patients with lung cancers is unknown.

Methods

We carried out this territory-wide, retrospective cohort study of 279,894 IHD patients prescribed with trimetazidine or long-acting oral nitrates in Hong Kong (population coverage of 7.5 millions, January 1999 − December 2020). A total of 6561 patients with pre-existing or de novo lung cancers were identified. Clinical outcomes of all-cause mortality were longitudinally compared between lung cancer patients who received trimetazidine (n = 547) versus non-users (control, n = 6014).

Results

Over 902.9 ± 1410.6 days, lower incidence of deaths occurred in the trimetazidine group (79.0 %, n = 432/547) compared to controls (90.5 %, n = 5442/6014, P < 0.001). Kaplan-Meier analyses showed that trimetazidine use was associated with significantly higher survival from all-cause mortality in IHD patients (trimetazidine: mean survival = 1840.6 [95 %CI 1596.0–2085.3], versus control: 1056.7 [95 %CI 1011.3–1102.0] days, Log Rank = 69.4, P < 0.001). Cox regression showed that trimetazidine use was significantly associated with reduced risk of all-cause mortality in crude (HR = 0.60 [95 %CI: 0.53 to 0.68], P < 0.001) and multivariable models (HR = 0.65 [95 % CI: 0.57 to 0.74], P < 0.001). Pre-specified analyses amongst patients with pre-existing lung cancers yielded similar findings (HR = 0.49 [95 %CI: 0.35 to 0.67], P < 0.001). Survival benefits related to trimetazidine use was predominantly restricted to non-cardiovascular mortality (P < 0.001).

Conclusions

Trimetazidine use is associated with higher overall survival in IHD patients with lung cancers, particularly from non-cardiovascular death. These findings need to be confirmed by randomized controlled trials.
背景在肺癌细胞中观察到了优先脂肪酸氧化的代谢重新布线。使用曲美他嗪这种抑制脂肪酸氧化的抗心绞痛药物是否会改变患有肺癌的缺血性心脏病(IHD)患者的临床预后尚不清楚。方法我们在全港范围内开展了这项回顾性队列研究,研究对象是香港279894名处方曲美他嗪或长效口服硝酸盐类药物的缺血性心脏病患者(1999年1月至2020年12月,覆盖人口750万)。研究共发现 6561 名原有或新发肺癌患者。结果在 902.9 ± 1410.6 天内,曲美他嗪组的死亡发生率(79.0%,n = 432/547)低于对照组(90.5%,n = 5442/6014,P < 0.001)。Kaplan-Meier 分析显示,使用曲美他嗪可显著提高 IHD 患者的全因死亡率生存率(曲美他嗪:平均生存率 = 1840.6 [95 %CI 1596.0-2085.3] 天,对照组:1056.7 [95 %CI 1011.3-1102.0] 天,Log Rank = 69.4,P <0.001)。Cox 回归显示,在粗略模型(HR = 0.60 [95 %CI: 0.53 to 0.68],P < 0.001)和多变量模型(HR = 0.65 [95 %CI: 0.57 to 0.74],P < 0.001)中,使用曲美他嗪与全因死亡风险的降低显著相关。对已有肺癌的患者进行预先指定的分析也得出了类似的结果(HR = 0.49 [95 %CI: 0.35 to 0.67], P <0.001)。与使用曲美他嗪相关的生存获益主要限于非心血管死亡(P <0.001)。结论使用曲美他嗪与患有肺癌的 IHD 患者总生存率的提高有关,尤其是非心血管死亡。这些发现需要通过随机对照试验加以证实。
{"title":"Treatment with trimetazidine dihydrochloride and lung cancer survival: Implications on metabolic re-programming","authors":"Yap-Hang Chan ,&nbsp;Cheng Yuen-Ting ,&nbsp;Chun-Fung Sin ,&nbsp;Edmond S.K. Ma ,&nbsp;Stephen T.S. Lam ,&nbsp;Shiu-Lun Au Yeung ,&nbsp;Bernard M.Y. Cheung ,&nbsp;Chung-Man Ho ,&nbsp;Kai-Hang Yiu ,&nbsp;Hung-Fat Tse","doi":"10.1016/j.lungcan.2024.107996","DOIUrl":"10.1016/j.lungcan.2024.107996","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic re-wiring with preferential fatty acid oxidation has been observed in lung cancer cells. Whether the use of trimetazidine, an anti-anginal agent that inhibits fatty acid oxidation, alters clinical outcomes in ischemic heart disease (IHD) patients with lung cancers is unknown.</div></div><div><h3>Methods</h3><div>We carried out this territory-wide, retrospective cohort study of 279,894 IHD patients prescribed with trimetazidine or long-acting oral nitrates in Hong Kong (population coverage of 7.5 millions, January 1999 − December 2020). A total of 6561 patients with pre-existing or <em>de novo</em> lung cancers were identified. Clinical outcomes of all-cause mortality were longitudinally compared between lung cancer patients who received trimetazidine (n = 547) versus non-users (control, n = 6014).</div></div><div><h3>Results</h3><div>Over 902.9 ± 1410.6 days, lower incidence of deaths occurred in the trimetazidine group (79.0 %, n = 432/547) compared to controls (90.5 %, n = 5442/6014, <em>P &lt; 0.001</em>). Kaplan-Meier analyses showed that trimetazidine use was associated with significantly higher survival from all-cause mortality in IHD patients (trimetazidine: mean survival = 1840.6 [95 %CI 1596.0–2085.3], versus control: 1056.7 [95 %CI 1011.3–1102.0] days, Log Rank = 69.4, <em>P &lt; 0.001</em>). Cox regression showed that trimetazidine use was significantly associated with reduced risk of all-cause mortality in crude (HR = 0.60 [95 %CI: 0.53 to 0.68], <em>P &lt; 0.001</em>) and multivariable models (HR = 0.65 [95 % CI: 0.57 to 0.74], <em>P &lt; 0.001</em>). Pre-specified analyses amongst patients with pre-existing lung cancers yielded similar findings (HR = 0.49 [95 %CI: 0.35 to 0.67], <em>P &lt; 0.001</em>). Survival benefits related to trimetazidine use was predominantly restricted to non-cardiovascular mortality (<em>P &lt; 0.001</em>).</div></div><div><h3>Conclusions</h3><div>Trimetazidine use is associated with higher overall survival in IHD patients with lung cancers, particularly from non-cardiovascular death. These findings need to be confirmed by randomized controlled trials.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107996"},"PeriodicalIF":4.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142529137","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
PRIMALung (EORTC-1901): PRophylactic cerebral irradiation (PCI) or active brain MAgnetic resonance imaging (MRI) surveillance in small-cell lung cancer (SCLC) patients PRIMALung(EORTC-1901):小细胞肺癌(SCLC)患者的预防性脑照射(PCI)或主动脑磁共振成像(MRI)监测。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.lungcan.2024.107993
Antonin Levy , Thierry Berghmans , Michael Koller , Beatrice Fournier , Murielle Mauer , Nicolaus Andratschke , Corinne Faivre-Finn
The PRIMALung EORTC-1901 trial investigates brain MRI ± PCI in all-stages of SCLC, aiming for non-inferior survival, improve cognition in the era of immunotherapy.
@finn_corinne
PRIMALung EORTC-1901 试验研究了所有阶段 SCLC 的脑 MRI 和 PCI,目的是在免疫疗法时代实现非劣效期生存并改善认知。@finn_corinne.
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引用次数: 0
Confronting synchronous multiple primary lung cancers: Navigating the intersection of challenges and opportunities 面对同步多发性原发性肺癌:挑战与机遇并存。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-22 DOI: 10.1016/j.lungcan.2024.107994
Xue He , Zhihui Yang , Fang Wu , Qingchun Liang , Wenliang Liu , Fenglei Yu , Chen Chen
The increased detection of synchronous multiple primary lung cancers (sMPLC) through advanced computed tomography underscores the necessity for innovative therapeutic approaches. sMPLC typically manifests as ground-glass opacities, mixed ground-glass opacities, and/or solid nodules, predominantly in early-stage, non-smoking female patients, with a majority being adenocarcinomas. The high prevalence of EGFR mutations and considerable heterogeneity among lesions pose distinct diagnostic and therapeutic challenges for sMPLC. This study provides a comprehensive review and analysis of recent clinical and radiological studies, genomic profiling, and the efficacy of the “Surgery + X” treatment model for sMPLC. Additionally, the article discusses several intricate and complex sMPLC cases, shedding light on the disease’s complexities and identifying existing gaps and potential breakthroughs in clinical diagnosis, treatment, and research. It underscores the critical role of a multidisciplinary approach and advocates for targeted research on sMPLC, highlighting its potential to impact lung cancer research significantly.
同步多发性原发性肺癌(sMPLC)通过先进的计算机断层扫描发现的病例越来越多,这凸显了创新治疗方法的必要性。sMPLC通常表现为磨玻璃不透明、混合磨玻璃不透明和/或实性结节,主要发生在早期非吸烟女性患者中,其中大多数为腺癌。表皮生长因子受体(EGFR)突变的高发生率和病变间的显著异质性为sMPLC的诊断和治疗带来了独特的挑战。本研究全面回顾和分析了最近的临床和放射学研究、基因组剖析以及 "手术+X "治疗模式对sMPLC的疗效。此外,文章还讨论了几个错综复杂的 sMPLC 病例,揭示了该疾病的复杂性,找出了临床诊断、治疗和研究方面的现有差距和潜在突破。文章强调了多学科方法的关键作用,并倡导对sMPLC进行有针对性的研究,突出了其对肺癌研究产生重大影响的潜力。
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引用次数: 0
Segmentectomy vs. Lobectomy in stage IA non-small cell lung cancer: A systematic review and meta-analysis of perioperative and survival outcomes IA期非小细胞肺癌的分段切除术与肺叶切除术:围手术期和生存结果的系统回顾和荟萃分析。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-21 DOI: 10.1016/j.lungcan.2024.107990
Luca Bertolaccini , Antonino Carmelo Tralongo , Marzia Del Re , Francesco Facchinetti , Roberto Ferrara , Tindara Franchina , Paolo Graziano , Umberto Malapelle , Jessica Menis , Antonio Passaro , Sara Pilotto , Sara Ramella , Giulio Rossi , Rocco Trisolini , Michela Cinquini , Francesco Passiglia , Silvia Novello
While recent randomized controlled trials (RCT) have suggested superior overall survival (OS) outcomes with segmentectomy over lobectomy, questions remain regarding the comparability of these surgical procedures for treating early-stage non-small cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to synthetize existing evidence and to compare the survival outcomes observed for stage IA NSCLC following segmentectomy or lobectomy.
40 studies (38 observational, 2 RCTs) encompassing 103,926 patients were analyzed. Primary outcomes included overall survival (OS), disease-free survival (DFS), local recurrences, harvested lymph nodes, postoperative morbidity, and length of hospital stay. Risk of bias was assessed using established tools, and evidence certainty was evaluated using GRADE.
Non-RCTs showed an OS HR of 1.10 (95 % CI: 0.94–1.30, p = 0.24) with low certainty, contrasting with RCTs’ HR of 0.82 (95 % CI: 0.66–1.02, p = 0.7) with moderate certainty. Local recurrences exhibited OR 1.40 (95 % CI: 0.94–2.08, p = 0.09) in non-RCTs with low certainty, and RR 1.61 (95 % CI: 1.12–2.31, p = 0.01) in RCTs with low certainty. Non-RCTs showed DFS HR 1.13 (95 % CI: 0.95–1.34, p = 0.18) with low certainty, while RCTs yielded HR 1.00 (95 % CI: 0.85–1.18, p = 0.97) with moderate certainty. Lobectomy resulted in more harvested lymph nodes. Postoperative morbidity and length of hospital stay did not differ significantly.
While definitive evidence for OS, DFS, and postoperative outcomes differences was inconclusive, a potential increase in local recurrences following lobectomy was noted. Further well-designed studies are warranted to enhance evidence and inform clinical practice in stage I lung cancer surgery.
虽然最近的随机对照试验(RCT)表明,分段切除术的总生存期(OS)结果优于肺叶切除术,但这些手术方法在治疗早期非小细胞肺癌(NSCLC)方面的可比性仍存在疑问。本系统综述和荟萃分析旨在综合现有证据,比较分段切除术或肺叶切除术治疗IA期NSCLC的生存效果。共分析了 40 项研究(38 项观察性研究,2 项 RCT 研究),涉及 103,926 名患者。主要结果包括总生存期(OS)、无病生存期(DFS)、局部复发、摘除淋巴结、术后发病率和住院时间。偏倚风险采用既定工具进行评估,证据确定性采用 GRADE 进行评估。非研究性试验显示,OS HR 为 1.10(95 % CI:0.94-1.30,p = 0.24),确定性较低,而研究性试验的 HR 为 0.82(95 % CI:0.66-1.02,p = 0.7),确定性中等。局部复发在确定性较低的非研究性试验中表现为 OR 1.40(95 % CI:0.94-2.08,p = 0.09),在确定性较低的研究性试验中表现为 RR 1.61(95 % CI:1.12-2.31,p = 0.01)。非研究性试验的 DFS HR 为 1.13(95 % CI:0.95-1.34,p = 0.18),确定性较低;而研究性试验的 HR 为 1.00(95 % CI:0.85-1.18,p = 0.97),确定性中等。肺叶切除术可收获更多淋巴结。术后发病率和住院时间差异不大。虽然 OS、DFS 和术后结果差异的确切证据尚不确定,但注意到肺叶切除术后局部复发可能会增加。有必要进一步开展设计良好的研究,以增强证据并为 I 期肺癌手术的临床实践提供参考。
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Lung Cancer
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