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Lung cancer survival trends and prognostic factors: A 26-year population-based study in Girona Province, Spain 肺癌的生存趋势和预后因素:西班牙赫罗纳省一项为期 26 年的人口研究。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-20 DOI: 10.1016/j.lungcan.2024.107995
Eduard Teixidor-Vilà , Jan Trallero , Montse Puigdemont , Anna Vidal-Vila , Alejandro Hernandez-Martínez , Elia Sais , Josep Sabaté-Ortega , Sara Verdura , Javier A. Menendez , Joaquim Bosch-Barrera , Arantza Sanvisens , Rafael Marcos-Gragera

Background

Lung cancer (LC) is Europe’s primary cause of cancer-related mortality largely due to its historically low survival rates. The aim of this study was to analyze 26-year survival trends in the province of Girona, Spain, and to identify key prognostic factors.

Methods

Population-based study of LC cases collected between 1994 and 2019, with follow-up until December 31, 2021. Variables included date of diagnosis, sex, age, histology, and tumor stage (the latter since 2010). Diagnosis dates were categorized into three periods (1994–2002, 2003–2011, and 2012–2019). Multivariate flexible parametric models, incorporating age as a non-linear, time-varying covariate, were used to analyze net survival (NS) and trends. Annual absolute change in survival (AAC_S) was calculated using 3-year NS.

Results

The analysis of 9,113 LC cases showed a NS improvement between the first and last period (7.1 months (95 %CI: 6.5;7.6) to 8.5 months (95 %CI: 7.9;9.1)). Squamous cell carcinoma (NSC-SCC) showed the greatest improvement with an AAC_S of 0.32 % (95 % CI: 0.21; 0.43), while survival for non-small cell lung cancer not otherwise specified declined (AAC_S of −0.19 % (95 %CI: −0.26; −0.12)). Prognostic analysis of the 3,642 cases (2010–2019) indicated a lower LC death risk for adenocarcinoma and NSC-SCC compared to LC not otherwise specified (HR 0.52 and 0.62, respectively). Increasing tumor stage correlated with higher LC mortality risk (1.8-, 4.0-, and 10.1-fold increase for stage II, III, and IV, respectively, compared to stage I).

Conclusions

LC survival has notably improved, particularly for NSC-SCC. Survival is influenced by sex, age, date of diagnosis, tumor histology and especially by stage, underscoring comprehensive data collection’s importance.
背景:肺癌(LC)是欧洲癌症相关死亡的主要原因,这主要是因为肺癌的存活率历来较低。本研究旨在分析西班牙赫罗纳省 26 年的生存趋势,并确定关键的预后因素:方法:对 1994 年至 2019 年间收集的 LC 病例进行基于人口的研究,随访至 2021 年 12 月 31 日。变量包括诊断日期、性别、年龄、组织学和肿瘤分期(后者自 2010 年起)。诊断日期分为三个时期(1994-2002 年、2003-2011 年和 2012-2019 年)。多变量灵活参数模型将年龄作为非线性时变协变量,用于分析净生存率(NS)和趋势。每年生存率的绝对变化(AAC_S)以3年净生存率计算:结果:对 9113 例 LC 病例的分析表明,NS 在第一阶段和最后阶段之间有所改善(7.1 个月(95 %CI:6.5;7.6)至 8.5 个月(95 %CI:7.9;9.1))。鳞状细胞癌(NSC-SCC)的生存期改善幅度最大,AAC_S 为 0.32 % (95 %CI: 0.21; 0.43),而未作其他说明的非小细胞肺癌的生存期则有所下降(AAC_S 为 -0.19 % (95 %CI: -0.26; -0.12))。对 3,642 例病例(2010-2019 年)进行的预后分析表明,腺癌和非小细胞肺癌的 LC 死亡风险低于非特异性 LC(HR 分别为 0.52 和 0.62)。肿瘤分期的增加与LC死亡风险的增加相关(与I期相比,II期、III期和IV期的LC死亡风险分别增加了1.8倍、4.0倍和10.1倍):结论:LC 的生存率显著提高,尤其是 NSC-SCC 的生存率。生存率受性别、年龄、诊断日期、肿瘤组织学,尤其是分期的影响,这凸显了全面数据收集的重要性。
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引用次数: 0
CD8+ T cells infiltrating into tumors were controlled by immune status of pulmonary lymph nodes and correlated with non-small cell lung cancer (NSCLC) patients’ prognosis treated with chemoimmunotherapy 浸润肿瘤的 CD8+ T 细胞受肺部淋巴结免疫状态的控制,并与接受化疗免疫疗法的非小细胞肺癌(NSCLC)患者的预后相关。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-15 DOI: 10.1016/j.lungcan.2024.107991
Zhexin Bai , Xu Cheng , Tianyu Ma , Gege Li , Xiaojue Wang , Ziyu Wang , Ling Yi , Zhidong Liu

Purpose

Neoadjuvant chemoimmunotherapy has the potential to reduce tumor burden, improve the pathological complete response (pCR) rate, and significantly prolong patients’ disease-free survival (DFS). However, the treatment’s effectiveness varies among NSCLC patients. The immunological mechanisms contributing to tumor regression still require further exploration and elucidation.

Methods

The immune status of patients’ local tumor microenvironment (TME) before and after neoadjuvant chemoimmunotherapy, their paired pulmonary lymph nodes (11th LNs) after therapy, including infiltrating immune cell densities and their correlations, were analyzed using multiplex immunofluorescence.

Results

Fifty-six NSCLC patients undergoing neoadjuvant chemoimmunotherapy were enrolled and subsequently underwent surgical resection and pathological evaluation. Among these, 19 patients achieved a pCR, 6 patients exhibited a major pathological response (MPR), and 31 patients did not achieve MPR. There were no significant difference in the densities of CD8+ T cell, Treg and Dendritic cell (DC) in patients’ TME before neoadjuvant therapy (n = 26, P = 0.091, P = 0.753, P = 0.905, respectively), but after treament, these immune cells’ dynamics were significantly different between different response group. CD8+ T cell densities were increased in pCR gourp (P = 0.006), but not in non-pCR group (P = 0.389); the densities of Treg were increased in non-pCR gourp (P = 0.0004), but DC were significantly decreased in non-pCR gourp (P = 0.005). After surgery, the TME were also significantly different: patients achieving pCR typically demonstrated high densities of CD8+ T cell, DC and low densities of Tregs (P = 0.0001, P < 0.0001 and P = 0.0004). The immune status of 11th LNs also exhibited significant differences. DC densities were much higher in pCR patients, whereas Treg in the pCR group were significantly lower than those in the non-pCR group (P = 0.0008 and P = 0.003). Furthermore, the densities of DC in the TME showed a moderate positive correlation with DC in 11th LNs (P = 0.0002), while the densities of Tregs in the TME exhibited a moderate negative correlation with DC densities in 11th LNs (P = 0.03). Patients who had high densities of CD8+ T cell in the resection tissues and DC in the LNs, experienced longer DFS (P = 0.048 and P = 0.024).

Conclusion

Immune cells in both pulmonary LNs and the TME collectively influence the remodeling of the NSCLC patient’s TME, thus impacting treatment response and prognosis.
目的:新辅助化疗免疫疗法有望减轻肿瘤负荷,提高病理完全反应率(pCR),并显著延长患者的无病生存期(DFS)。然而,NSCLC 患者的治疗效果各不相同。导致肿瘤消退的免疫学机制仍需进一步探索和阐明:方法:采用多重免疫荧光技术分析了新辅助化疗免疫治疗前后患者局部肿瘤微环境(TME)的免疫状态、治疗后配对肺淋巴结(第11淋巴结)的免疫状态,包括浸润免疫细胞密度及其相关性:56名接受新辅助化疗免疫治疗的NSCLC患者被纳入研究,随后接受了手术切除和病理评估。其中,19 例患者获得 pCR,6 例患者获得主要病理反应(MPR),31 例患者未获得 MPR。新辅助治疗前,患者TME中的CD8+ T细胞、Treg和树突状细胞(DC)密度无明显差异(分别为26人,P=0.091,P=0.753,P=0.905),但治疗后,这些免疫细胞的动态变化在不同反应组间有明显差异。CD8+ T细胞的密度在pCR瓠果中有所增加(P = 0.006),但在非PCR组中没有增加(P = 0.389);Treg的密度在非PCR瓠果中有所增加(P = 0.0004),但在非PCR瓠果中DC明显减少(P = 0.005)。手术后,TME 也有显著差异:获得 pCR 的患者通常表现出 CD8+ T 细胞、DC 的高密度和 Treg 的低密度(P = 0.0001,P 结论):肺LN和TME中的免疫细胞共同影响NSCLC患者TME的重塑,从而影响治疗反应和预后。
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引用次数: 0
Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia 免疫检查点抑制剂联合铂类化疗作为HER2突变非小细胞肺癌患者一线治疗的疗效:LC-SCRUM-Asia的研究结果
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-13 DOI: 10.1016/j.lungcan.2024.107992
Yuki Kato , Hibiki Udagawa , Shingo Matsumoto , Hiroki Izumi , Yuichiro Ohe , Terufumi Kato , Kazumi Nishino , Shingo Miyamoto , Sachiko Kawana , Kenichi Chikamori , Masato Shingyoji , Yuki Sato , Yuji Takada , Ryo Toyozawa , Koichi Azuma , Yu Tanaka , Tetsuya Sakai , Yuji Shibata , Eri Sugiyama , Kaname Nosaki , Koichi Goto

Introduction

HER2 mutations are reported to occur in 2%–5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with HER2-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear.

Methods

Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with HER2-mutant NSCLC were investigated.

Results

Of the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor HER2 mutations were detected in 402 patients (2.6 %). The most common subtype of HER2 mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring HER2 mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring EGFR mutations or ALK fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50–0.88]; P < 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57–1.12], P = 0.20).

Conclusions

Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs.
导言据报道,在所有非小细胞肺癌(NSCLC)病例中,有2%-5%发生了HER2突变。HER2突变的NSCLC患者在接受免疫检查点抑制剂(ICIs)加铂类化疗作为一线治疗后的临床疗效仍不明确。结果 在LC-SCRUM-Asia数据库登记的15251名NSCLC患者中,有402名患者(2.6%)检测到肿瘤HER2突变。最常见的HER2突变亚型是外显子20框架内插入(79%),其次是外显子20ins以外的酪氨酸激酶结构域突变(10%)和胞外结构域突变(7%)。与携带表皮生长因子受体(EGFR)突变或ALK融合的NSCLC相比,携带HER2突变的NSCLC显示出更高的肿瘤突变负荷(TMB)(中位数:每兆碱基突变数分别为4.22对2.54和2.52)。在402名患者中,有268名患者接受了以铂为基础的化疗,同时使用ICIs(Chemo-ICI,n = 95)或不使用ICIs(Chemo-alone,n = 173)作为一线治疗。与单用化疗组相比,化疗-ICI 组的无进展生存期(PFS)明显更长(中位 8.5 个月对 6.3 个月;HR [95 %CI]:0.66 [0.50-0.88];P < 0.005)。多变量分析发现,在铂类化疗基础上使用 ICIs 是 PFS 的独立有利预后因素。化疗组和单用化疗组患者的总生存期无明显差异(中位 31.1 个月 vs. 23.3 个月;HR [95 %CI]:0.80 [0.57-1.12],P = 0.20)。在铂类化疗中加入 ICIs 可改善 HER2 突变 NSCLC 患者的 PFS,TMB 相对较高可能与 HER2 突变 NSCLC 患者接受 ICIs 化疗的 PFS 延长有关。
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引用次数: 0
Reassessing pembrolizumab dosing in NSCLC for methodological and clinical accuracy 重新评估 NSCLC 中 pembrolizumab 剂量的方法学和临床准确性
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.lungcan.2024.107989
Da Qiu , Chao Qiu , Yongneng Wang , Dan Shan
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引用次数: 0
Afatinib plus bevacizumab combination after osimertinib resistance in advanced EGFR-mutant non-small cell lung cancer: Phase II ABCD-study 晚期表皮生长因子受体突变非小细胞肺癌患者对奥希替尼耐药后的阿法替尼加贝伐珠单抗联合治疗:II期ABCD研究。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.lungcan.2024.107988
Akito Hata , Nobuyuki Katakami , Naoto Takase , Kayoko Kibata , Yuta Yamanaka , Motohiro Tamiya , Masahide Mori , Takashi Kijima , Satoshi Morita , Kazuko Sakai , Kazuto Nishio

Introduction

Many clinical studies showed a synergy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor inhibitors. We hypothesized afatinib plus bevacizumab exerts clinical potency after developing various osimertinib resistant mechanisms.

Methods

EGFR-mutant non-small cell lung cancer patients were enrolled after osimertinib resistance. Afatinib at 30–40 mg/day and bevacizumab at 15 mg/kg tri-weekly were administered until progression. Plasma/histologic rebiopsied samples after osimertinib failure were analyzed to examine resistant mechanisms: gene alterations/copy-number gain using cancer personalized profiling by deep sequencing.

Results

Between January 2018 and October 2020, 28 patients were enrolled. Response and disease control rates were 17.9 % and 78.6 %, respectively. Median duration of response was 9.0 (range, 4.2–22.3) months. Median progression-free and overall survivals were 2.7 and 9.3 months, respectively. Twenty-eight (100 %) plasma and/or 21 (75 %) histologic rebiopsies identified: 17 (61 %) TP53; 15 (54 %) T790M; 9 (32 %) uncommon EGFR; 9 (32 %) MET; 6 (21 %) C797S; 3 (11 %) BRAF; 2 (7 %) HER2; 2 (7 %) KRAS; and 2 (7 %) PI3K mutations. One (17 %) of 6 C797S patients showed complete response. Three (33 %) of 9 uncommon EGFR-mutated patients achieved radiographic response. Neither 15 T790M-positive nor 6 EGFR downstream signaling mutations: BRAF; KRAS; or PI3K-positive patients responded, but 5 (38 %) of 13 T790M-negative patients responded. Adverse events ≥ grade 3 and incidence ≥ 5 % were: hypertension (29 %); proteinuria (7 %); and diarrhea (7 %). There were neither treatment-related death nor interstitial lung disease.

Conclusions

Selected population could obtain clinical benefit from afatinib plus bevacizumab, based on rebiopsy results after osimertinib resistance.
导言:许多临床研究表明,表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)和血管内皮生长因子抑制剂具有协同作用。我们假设阿法替尼加贝伐珠单抗在发展出各种奥希替尼耐药机制后能发挥临床疗效:我们招募了奥希替尼耐药后的表皮生长因子受体突变非小细胞肺癌患者。阿法替尼30-40毫克/天,贝伐单抗15毫克/千克,三周一次,直至病情进展。对奥希替尼耐药后的血浆/组织学重检样本进行了分析,以研究耐药机制:利用深度测序的癌症个性化图谱分析基因改变/拷贝数增加:2018年1月至2020年10月,28名患者入组。应答率和疾病控制率分别为17.9%和78.6%。中位应答持续时间为 9.0 个月(4.2-22.3 个月)。无进展生存期和总生存期的中位数分别为 2.7 个月和 9.3 个月。28例(100%)血浆和/或21例(75%)组织学重新活检结果表明:17例(61%)TP53;15例(54%)T790M;9例(32%)不常见的表皮生长因子受体(EGFR);9例(32%)MET;6例(21%)C797S;3例(11%)BRAF;2例(7%)HER2;2例(7%)KRAS;2例(7%)PI3K突变。6 名 C797S 患者中有 1 名(17%)完全应答。在 9 名不常见的表皮生长因子受体突变患者中,有 3 人(33%)获得了放射学反应。15 例 T790M 阳性患者和 6 例表皮生长因子受体下游信号突变患者均未获得完全应答:BRAF、KRAS或PI3K阳性患者均无反应,但13例T790M阴性患者中有5例(38%)有反应。≥3级且发生率≥5%的不良反应有:高血压(29%)、蛋白尿(7%)和腹泻(7%)。没有出现与治疗相关的死亡或间质性肺病:结论:根据奥希替尼耐药后的重新活检结果,阿法替尼加贝伐珠单抗可使部分人群获得临床获益。
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引用次数: 0
Crispr-mediated genome editing reveals a preponderance of non-oncogene addictions as targetable vulnerabilities in pleural mesothelioma Crispr 介导的基因组编辑揭示了胸膜间皮瘤中的非癌基因成瘾性是可靶向的薄弱环节。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.lungcan.2024.107986
Duo Xu , Shun-Qing Liang , Min Su , Haitang Yang , Rémy Bruggmann , Simone Oberhaensli , Zhang Yang , Yanyun Gao , Thomas M. Marti , Wenxiang Wang , Ralph A. Schmid , Yongqian Shu , Patrick Dorn , Ren-Wang Peng
Pleural mesothelioma (PM) is an aggressive cancer with limited treatment options. In particular, the frequent loss of tumor suppressors, a key oncogenic driver of the disease that is therapeutically intractable, has hampered the development of targeted cancer therapies. Here, we interrogate the PM genome using CRISPR-mediated gene editing to systematically uncover PM cell susceptibilities and provide an evidence-based rationale for targeted cancer drug discovery. This analysis has allowed us to identify with high confidence numerous known and novel gene dependencies that are surprisingly highly enriched for non-oncogenic pathways involved in response to various stress stimuli, in particular DNA damage and transcriptional dysregulation. By integrating genomic analysis with a series of in vitro and in vivo functional studies, we validate and prioritize several non-oncogene addictions conferred by CDK7, CHK1, HDAC3, RAD51, TPX2, and UBA1 as targetable vulnerabilities, revealing previously unappreciated aspects of PM biology. Our findings support the growing consensus that stress-responsive non-oncogenic signaling plays a key role in the initiation and progression of PM and provide a functional blueprint for the development of unprecedented targeted therapies to combat this formidable disease.
胸膜间皮瘤(PM)是一种侵袭性癌症,治疗方案有限。尤其是肿瘤抑制因子的频繁缺失,是该病难以治疗的关键致癌驱动因素,阻碍了癌症靶向疗法的开发。在这里,我们利用 CRISPR 介导的基因编辑技术对原发性骨髓瘤基因组进行了研究,系统地发现了原发性骨髓瘤细胞的易感性,并为靶向抗癌药物的发现提供了循证依据。这项分析使我们能够高置信度地确定许多已知和新的基因依赖关系,这些基因依赖关系竟然高度富集于非致癌通路,这些通路涉及对各种应激刺激的反应,特别是 DNA 损伤和转录失调。通过将基因组分析与一系列体外和体内功能研究相结合,我们验证并优先考虑了 CDK7、CHK1、HDAC3、RAD51、TPX2 和 UBA1 所赋予的几种非致癌基因成瘾性,将其作为可靶向的脆弱性,揭示了 PM 生物学中以前未被认识到的方面。我们的发现支持了越来越多的共识,即应激反应性非致癌信号在原发性骨髓瘤的发生和发展过程中起着关键作用,并为开发前所未有的靶向疗法提供了功能蓝图,以防治这种可怕的疾病。
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引用次数: 0
Stereologic consequences of iatrogenic collapse: The morphology of adenocarcinoma in situ overlaps with invasive patterns. Proposal for a necessary modified classification of pulmonary adenocarcinomas 先天性塌陷的立体学后果:原位腺癌的形态与侵袭性腺癌的形态重叠。建议对肺腺癌进行必要的修改分类。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.lungcan.2024.107987
Federica Filipello , Hans Blaauwgeers , Birgit Lissenberg-Witte , Andreas Schonau , Claudio Doglioni , Gianluigi Arrigoni , Teodora Radonic , Idris Bahce , Arthur Smit , Chris Dickhoff , Antonio Nuccio , Alessandra Bulotta , Yuko Minami , Masayuki Noguchi , Francesca Ambrosi , Erik Thunnissen
Recognizing non-invasive growth patterns is necessary for correct diagnosis, invasive size determination and pT-stage in resected non-small cell lung carcinoma. Due to iatrogenic collapse after resection, the distinction between adenocarcinoma in-situ (AIS) and invasive adenocarcinoma may be difficult. The aim of this study is to investigate the complex morphology of non-mucinous non-invasive patterns of AIS in resection specimen with iatrogenic collapse, and to relate this to follow-up.
The effects of iatrogenic collapse on the morphology of collapsed AIS were simulated in a mathematical model. Three dimensional related criteria applied in a modified classification, using also cytokeratin 7 and elastin as additional stains, in two independent retrospective cohorts of primary pulmonary adenocarcinomas ≤3 cm resection specimen with available follow-up information.
The model demonstrated that infolding of alveolar walls occurs during iatrogenic collapse and lead to a significant increase in tumor cell heights in maximal collapse areas, compared to less collapsed areas. The morphology of infolded AIS overlaps with patterns described as papillary and acinar adenocarcinoma according to the WHO classification, necessitating an adaptation.
The modified classification incorporates recognition of iatrogenic and biologic collapse, tangential cutting effect true invasion and surrogate markers of invasion i.e. grey zone, covering a multilayering falling short of micropapillary, cribriform and solid alveolar filling growth. The use of elastin and CK7 staining aids in the morphologic recognition of iatrogenic collapsed AIS and the distinction from invasive adenocarcinoma. Out of a total of 70 resection specimens 1 case was originally classified as AIS and 9 were reclassified as iatrogenic collapsed AIS. Patients with collapsed AIS showed a 100 % recurrence-free survival after a mean follow-up time of 69.5 months.
With the current WHO classification, AIS is overdiagnosed as invasive adenocarcinoma due to infolding. The modified classification facilitates the diagnosis of AIS.
要对切除的非小细胞肺癌进行正确诊断、确定浸润性大小和 pT 分期,就必须识别非浸润性生长模式。由于切除术后的先天性塌陷,原位腺癌(AIS)和浸润性腺癌可能难以区分。本研究的目的是调查非黏液性非浸润性 AIS 在先天性塌陷切除标本中的复杂形态,并将其与随访联系起来。通过数学模型模拟了先天性塌陷对塌陷 AIS 形态的影响。在两个独立的具有随访信息的原发性肺腺癌≤3厘米切除标本回顾性队列中,将三维相关标准应用于修正的分类中,同时使用细胞角蛋白7和弹性蛋白作为附加染色。该模型表明,肺泡壁在先天性塌陷过程中会发生内折,与塌陷程度较轻的区域相比,最大塌陷区域的肿瘤细胞高度会显著增加。内折 AIS 的形态与世卫组织分类中描述的乳头状腺癌和尖状腺癌的形态重叠,因此有必要进行调整。修改后的分类纳入了对先天性和生物性塌陷的认识、切向切割效应的真正侵袭和侵袭的替代标志物(即灰区),涵盖了微乳头状、楔形和实性肺泡填充生长的多层次缺失。使用弹性蛋白和 CK7 染色有助于从形态学上识别先天性塌陷性 AIS,并与浸润性腺癌相鉴别。在总共 70 例切除标本中,1 例最初被归类为 AIS,9 例被重新归类为先天性塌陷性 AIS。在平均 69.5 个月的随访时间后,塌陷型 AIS 患者的无复发生存率达到了 100%。按照目前的世卫组织分类法,AIS会因折叠而被过度诊断为浸润性腺癌。修改后的分类有助于 AIS 的诊断。
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引用次数: 0
Integrated analysis of older adults and patients with renal dysfunction in the IMpower130 and IMpower132 randomized controlled trials for advanced non-squamous non-small cell lung cancer 对IMpower130和IMpower132治疗晚期非鳞状非小细胞肺癌随机对照试验中的老年人和肾功能不全患者进行综合分析。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lungcan.2024.107859
Makoto Nishio , Satoshi Watanabe , Hibiki Udagawa , Naoko Aragane , Yuki Nakagawa , Yuki Kobayashi , Haruhiro Saito

Objectives

This exploratory integrated analysis of the randomized Phase III IMpower130 and IMpower132 trials evaluated the efficacy and safety of atezolizumab plus platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC) who were aged ≥75 years or had renal dysfunction.

Materials and methods

Chemotherapy-naïve patients with stage IV non-squamous NSCLC received atezolizumab-containing therapy or platinum-doublet chemotherapy in IMpower130 and IMpower132. This integrated analysis assessed efficacy (including overall survival [OS], progression-free survival [PFS], and objective response rates) and safety in the integrated population and in patients ≥75 years old. Subgroup analyses by baseline creatinine clearance (<45, 45 to <60, and ≥60 mL/min) were conducted for each study population.

Results

This integrated analysis included 1224 patients: 737 in the atezolizumab-containing group and 487 in the chemotherapy group. At data cutoff, the hazard ratio (HR) for PFS was 0.62 (95% CI: 0.54–0.71) in the integrated population and 0.59 (95% CI: 0.40–0.88) in the ≥75-years subgroup. The HR for OS was 0.81 (95% CI: 0.68–0.95) in the integrated population and 0.65 (95% CI: 0.39–1.07) in the ≥75-years subgroup. PFS and OS benefits with the atezolizumab combination vs chemotherapy were maintained across subgroups with varying renal function in IMpower130, and PFS benefits were maintained across subgroups in IMpower132.

Conclusions

The results of this post hoc integrated analysis of IMpower130 and IMpower132 show that the efficacy and safety of atezolizumab plus platinum-doublet chemotherapy is maintained in patients ≥75 years old and in patients with renal dysfunction.
研究目的这项对随机III期IMpower130和IMpower132试验的探索性综合分析评估了阿特珠单抗联合铂类化疗对年龄≥75岁或肾功能不全的非小细胞肺癌(NSCLC)患者的疗效和安全性:化疗无效的IV期非鳞癌NSCLC患者在IMpower130和IMpower132中接受了阿特珠单抗或铂类双联化疗。这项综合分析评估了综合人群和年龄≥75岁患者的疗效(包括总生存期[OS]、无进展生存期[PFS]和客观反应率)和安全性。根据基线肌酐清除率进行了分组分析(结果:基线肌酐清除率为0.5%的患者为1例,基线肌酐清除率为0.5%的患者为2例):该综合分析包括 1224 名患者:含阿替珠单抗组737例,化疗组487例。数据截止时,综合人群的 PFS 危险比(HR)为 0.62(95% CI:0.54-0.71),≥75 岁亚组的 PFS 危险比为 0.59(95% CI:0.40-0.88)。综合人群的OS HR为0.81(95% CI:0.68-0.95),≥75岁亚组的OS HR为0.65(95% CI:0.39-1.07)。在IMpower130中,阿特珠单抗联合化疗的PFS和OS获益在不同肾功能的亚组中保持不变,在IMpower132中,PFS获益在不同亚组中保持不变:结论:对IMpower130和IMpower132的事后综合分析结果表明,atezolizumab联合铂类双药化疗对年龄≥75岁的患者和肾功能不全患者的疗效和安全性保持不变。
{"title":"Integrated analysis of older adults and patients with renal dysfunction in the IMpower130 and IMpower132 randomized controlled trials for advanced non-squamous non-small cell lung cancer","authors":"Makoto Nishio ,&nbsp;Satoshi Watanabe ,&nbsp;Hibiki Udagawa ,&nbsp;Naoko Aragane ,&nbsp;Yuki Nakagawa ,&nbsp;Yuki Kobayashi ,&nbsp;Haruhiro Saito","doi":"10.1016/j.lungcan.2024.107859","DOIUrl":"10.1016/j.lungcan.2024.107859","url":null,"abstract":"<div><h3>Objectives</h3><div>This exploratory integrated analysis of the randomized Phase III IMpower130 and IMpower132 trials evaluated the efficacy and safety of atezolizumab plus platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC) who were aged ≥75 years or had renal dysfunction.</div></div><div><h3>Materials and methods</h3><div>Chemotherapy-naïve patients with stage IV non-squamous NSCLC received atezolizumab-containing therapy or platinum-doublet chemotherapy in IMpower130 and IMpower132. This integrated analysis assessed efficacy (including overall survival [OS], progression-free survival [PFS], and objective response rates) and safety in the integrated population and in patients ≥75 years old. Subgroup analyses by baseline creatinine clearance (&lt;45, 45 to &lt;60, and ≥60 mL/min) were conducted for each study population.</div></div><div><h3>Results</h3><div>This integrated analysis included 1224 patients: 737 in the atezolizumab-containing group and 487 in the chemotherapy group. At data cutoff, the hazard ratio (HR) for PFS was 0.62 (95% CI: 0.54–0.71) in the integrated population and 0.59 (95% CI: 0.40–0.88) in the ≥75-years subgroup. The HR for OS was 0.81 (95% CI: 0.68–0.95) in the integrated population and 0.65 (95% CI: 0.39–1.07) in the ≥75-years subgroup. PFS and OS benefits with the atezolizumab combination vs chemotherapy were maintained across subgroups with varying renal function in IMpower130, and PFS benefits were maintained across subgroups in IMpower132.</div></div><div><h3>Conclusions</h3><div>The results of this post hoc integrated analysis of IMpower130 and IMpower132 show that the efficacy and safety of atezolizumab plus platinum-doublet chemotherapy is maintained in patients ≥75 years old and in patients with renal dysfunction.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107859"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913174","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
Cryobiopsy versus fine-needle aspiration for shape-sensing robotic-assisted sampling of small lung nodules 形状感应机器人辅助肺部小结节取样的冷冻生物切片检查与细针穿刺术对比。
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lungcan.2024.107967
David Abia-Trujillo , Rodrigo Funes-Ferrada , Alejandra Yu Lee-Mateus , Alanna Barrios-Ruiz , Andras Khoor , Neal M. Patel , Britney N. Hazelett , Kelly S. Robertson , Sebastian Fernandez-Bussy

Introduction

Shape-sensing Robotic-assisted Bronchoscopy (ssRAB) has emerged as a promising tool for improved performance when sampling pulmonary nodules (PPN). Previous studies suggest that the 1.1 mm cryoprobe is as effective compared to fine needle aspiration (FNA), for different lesions sizes. We aim to compare the 1.1 mm cryoprobe performance to FNA for sampling PPN < 20 mm with ssRAB.

Material and Methods

We conducted a retrospective cohort study from November 2022 to February 2024 of patients who underwent ssRAB with cryobiopsy for evaluation of PPN. We compared the diagnostic yield and sensitivity for malignancy of cryobiopsy and FNA for the same PPN. Descriptive statistical analysis was conducted using the McNemar’s Test and Comparison of proportion. Multivariate logistic regression assessed the impact of PPN characteristics on the yield of each tool.

Results

We included 256 patients, with a combined 284 procedures, and 324 nodules sampled. The median maximum and minimum nodule size was 1.6 cm (IQR 1.17–2.4) and 1.17 cm (IQR 0.86–1.7) respectively. The overall ssRAB diagnostic yield was 93.8 % and sensitivity for malignancy was 97.5 %. Cryobiopsy had a diagnostic yield of 92 % and sensitivity of 96 %, FNA had a 70.4 % and 79.29 % respectively (P < 0.001). Cryobiopsy had a significantly higher performance compared to FNA across the analyzed categories (P < 0.05), except for the sensitivity of mixed-type lesions (P = 0.11). PPN < 10 mm and ≥ 10 mm − <15 mm sampled with FNA, had lower odds of achieving a diagnosis compared to the ≥ 20 mm group (OR = 0.305 IC95%: 0.142–0.65, p < 0.001; OR = 0.497 IC95%: 0.263–0.939, p = 0.031, respectively). Complications occurred in 5.98 % (N = 17) of cases.

Conclusion

Cryobiopsy demonstrates a statistically higher diagnostic yield and sensitivity for malignancy compared to FNA. Remarkably, FNA showed reduced diagnostic odds in PPN < 15 mm. ssRAB with cryobiopsy could enhance PPN diagnostic yield, leading to earlier lung cancer diagnosis and improve long-term survival rates.
简介形状感应机器人辅助支气管镜(ssRAB)已成为一种很有前途的工具,可提高肺结节(PPN)取样的效果。以前的研究表明,对于不同大小的病灶,1.1 毫米低温探针与细针抽吸(FNA)相比同样有效。我们的目的是比较 1.1 毫米冷冻探针与 FNA 在用 ssRAB 抽取小于 20 毫米的 PPN 时的性能:我们从 2022 年 11 月到 2024 年 2 月对接受 ssRAB 和冷冻活检评估 PPN 的患者进行了一项回顾性队列研究。我们比较了冷冻活检和 FNA 对相同 PPN 的诊断率和恶性肿瘤敏感性。我们使用 McNemar 检验和比例比较法进行了描述性统计分析。多变量逻辑回归评估了PPN特征对每种工具诊断率的影响:我们纳入了 256 名患者,共进行了 284 次手术,采集了 324 个结节样本。结节最大和最小尺寸的中位数分别为 1.6 厘米(IQR 1.17-2.4)和 1.17 厘米(IQR 0.86-1.7)。ssRAB的总体诊断率为93.8%,对恶性肿瘤的敏感性为97.5%。冷冻活组织检查的诊断率为 92%,灵敏度为 96%,FNA 的诊断率和灵敏度分别为 70.4% 和 79.29%(P 结论:冷冻活组织检查的诊断率和灵敏度均高于 FNA:与 FNA 相比,冷冻活组织检查对恶性肿瘤的诊断率和敏感性在统计学上更高。值得注意的是,FNA 对 PPN 的诊断几率较低。
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引用次数: 0
Can therapeutic drug monitoring of lorlatinib help us design the right CROWN? 罗拉替尼的治疗药物监测能否帮助我们设计出正确的 CROWN?
IF 4.5 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lungcan.2024.107965
Molly Li, Ross A. Soo
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引用次数: 0
期刊
Lung Cancer
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