Revue des Maladies Respiratoires Actualites最新文献

英文中文

Sommaire 摘要

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00051-5

引用次数: 0

Biomarqueurs tissulaires dans les CBNPC CBNCs中的组织生物标志物

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00058-8

A. Mansuet-Lupo , K. Leroy , M. Wislez

Tissue biomarkers play a central role in the management of non-small cell lung cancer (NSCLC). The evaluation of predictive biomarkers guides therapeutic decisions by enabling access to targeted therapies or immunotherapy, and forms the foundation of personalized medicine in oncology. The number of biomarkers has increased significantly since the discovery of EGFR gene mutations, due to the development of therapies targeting oncogenic drivers and antibody drug conjugates. These predictive biomarkers include, molecular alterations identified through sequencing (EGFR, BRAF, KRAS, ALK, ROSI, RET, MET, HER2, NTRK, NRG1), and protein biomarkers whose expression is assessed by immunohistochemistry (PD-L1, ALK, ROS1, NTRK, HER2, HER3, MET, TROP2, MTAP, CEACAM5). Testing recommendations in NSCLC are constantly evolving, and it is essential to stay up to date in order to propose the best treatment to each patient.

组织生物标志物在非小细胞肺癌（NSCLC）的治疗中起着核心作用。预测性生物标记物的评估通过获得靶向治疗或免疫治疗来指导治疗决策，并形成了肿瘤学个性化医疗的基础。自从发现EGFR基因突变以来，由于针对致癌驱动因素和抗体药物偶联物的治疗方法的发展，生物标志物的数量显著增加。这些预测性生物标志物包括通过测序确定的分子改变（EGFR、BRAF、KRAS、ALK、ROSI、RET、MET、HER2、NTRK、NRG1），以及通过免疫组织化学评估表达的蛋白质生物标志物（PD-L1、ALK、ROS1、NTRK、HER2、HER3、MET、TROP2、MTAP、CEACAM5）。NSCLC的检测建议是不断发展的，为了给每个患者提供最好的治疗，保持最新是至关重要的。

引用次数: 0

Le TNM : la 9e édition pour l'oncologie thoracique TNM：第9版乳腺肿瘤学

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00060-6

A. Agrafiotis , B. Grigoriu , P. Van Schil

The 9^th TNM edition for lung cancer is based on a database of 124,581 cases, of which 18.9% were entered prospectively. Regarding the T component no changes are implemented as the 8^th edition descriptors performed well in the new database. Concerning the N component, N2 is subdivided into N2a and N2b representing single station and multiple stations N2 involvement, respectively. Individual lymph nodes in each station are not counted. With regard to the M component, M1c is subdivided into M1c1 and M1c2 when multiple extrathoracic metastases are present in a single organ system or multiple organ systems, respectively. Bone and muscle are counted as a single organ system. Especially the new N descriptors have an impact on the overall stage groupings, whereby e.g. T1N1 belongs to stage IIA and T1N2a to stage IIB. M1c1 and M1c2 both belong to stage IVB.

For staging of thymic epithelial tumours comprising thymoma and thymic carcinoma, the 9^th edition is based on analysis of 9,147 cases. Changes are only proposed in the T component: T1a characterizes tumors until 5 cm and T1b tumors larger than 5 cm in greatest dimension. T2 denotes partial or full-thickness pericardial invasion but also direct invasion into lung parenchyma or phrenic nerve. Invasion of mediastinal pleura is now separately considered as additional histologic descriptor. There are no changes in the stage groupings with both T1a and T1b belonging to stage I.

Regarding pleural mesothelioma, after analysis of a database of 3,481 cases, important changes are proposed for the clinical T descriptors and no changes are implemented for the N and M descriptors. Maximal pleural thickness is now measured at 3 levels on axial CT slices: at upper, middle and lower chest and a sum of the 3 measurements is made (Psum). On a sagittal image maximal pleural thickness in the fissure is measured as Fmax. Cut-off values for Psum are 12 and 30 mm, and for Fmax 5 mm. These will finally determine the specific T-category. For a pathologist it is not possible to perform exactly the same measurements on a resected specimen and for this reason, only the clinical stage groupings were redefined without any changes in the pathological stage groupings. 1877-1203/© 2025 SPLF. Published by Elsevier Masson SAS. All rights reserved.

第9版肺癌TNM基于124581例病例的数据库，其中18.9%是前瞻性输入的。关于T组件，没有实现任何更改，因为第8版描述符在新数据库中表现良好。对于N分量，N2细分为N2a和N2b，分别代表单站和多站N2参与。每个站点的单个淋巴结不计算在内。对于M成分，当多发胸外转移灶出现在单一器官系统或多器官系统时，M1c可细分为M1c1和M1c2。骨骼和肌肉被认为是一个单一的器官系统。特别是新的N描述符对整体阶段分组产生了影响，例如T1N1属于IIA阶段，T1N2a属于IIB阶段。M1c1和M1c2都属于IVB期。对于胸腺上皮肿瘤的分期，包括胸腺瘤和胸腺癌，第9版是基于对9147例病例的分析。仅在T分量中提出了变化：T1a表征肿瘤至5cm， T1b肿瘤最大尺寸大于5cm。T2表示部分或全层心包侵犯，也可直接侵犯肺实质或膈神经。纵隔胸膜的侵犯现在被单独认为是附加的组织学描述。对于胸膜间皮瘤，在分析了3481例病例的数据库后，对临床T描述符进行了重要的修改，对N和M描述符没有进行修改。现在在轴向CT切片上测量3个级别的最大胸膜厚度：上、中、下胸部，并将3个测量值相加（Psum）。在矢状面图像上，裂隙中的最大胸膜厚度测量为Fmax。Psum的截止值为12和30毫米，Fmax为5毫米。这些将最终确定具体的t类。对于病理学家来说，不可能对切除的标本进行完全相同的测量，因此，只有临床分期分组被重新定义，而病理分期分组没有任何变化。1877-1203/©2025 splf。Elsevier Masson SAS出版。版权所有。

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引用次数: 0

Cancer bronchique non à petites cellules avec autres mutations actionnables (BRAF, MET, HER2) 非小细胞肺癌（BRAF， MET, HER2）

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00079-5

A. Mogenet , A. Cortot , P. Abdayem , D. Planchard , L. Greillier

Non-Small Cell Lung Cancer (NSCLC) outcomes has been significantly improved since the discovery of oncogenic driver alterations and implementation of targeted therapies such as tyrosine kinase inhibitors, antibody drug conjugates or bispecific antibodies. Nowadays, wild molecular profiling, preferably with next-generation sequencing panels is crucial before starting treatment in patients with non-squamous NSCLC regardless of their smoking status, and in those with squamous NSCLC who are little or non-smokers, on tissue samples but also liquid biopsies that can tremendously helpful despite their lack of sensitivity. In this review, we will present the latest evidence on some rare molecular alterations, BRAF, MET and HER2, with constant innovation pipeline. Even if many of these new drugs are still not funded in Europe, clinical trials enrollment allows our patients to benefit from innovative treatments and generate data. Translational research programs with repeat samples are also important to explore mechanisms of resistance to these new drugs.

非小细胞肺癌（NSCLC）的预后已经显著改善，因为发现了致癌驱动改变和实施靶向治疗，如酪氨酸激酶抑制剂，抗体药物偶联物或双特异性抗体。如今，在非鳞状NSCLC患者开始治疗之前，无论其吸烟状况如何，以及在很少或不吸烟的鳞状NSCLC患者中，组织样本和液体活检都是至关重要的，尽管它们缺乏敏感性，但野生分子谱分析，最好是使用下一代测序面板。在这篇综述中，我们将介绍一些罕见的分子改变，BRAF， MET和HER2的最新证据，并不断创新。即使这些新药中有许多还没有在欧洲获得资助，临床试验的登记可以让我们的病人从创新治疗中受益，并产生数据。重复样本的转化研究项目对于探索对这些新药的耐药性机制也很重要。

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引用次数: 0

Prise en charge des cancers bronchiques à petites cellules de stade localisé : actualisation 局部小细胞肺癌的管理：更新

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00081-3

S. Thureau , E. Nicolas , C. Faivre-Finn , E. Giroux Leprieur , S. Ocak , P. Fournel , E. Negre , B. Roch , C. Le Péchoux

Limited-stage small cell lung cancer (LS-SCLC) represents 10-15% of all lung cancers, and because of its rapid tumor kinetics, less than a third of SCLC are discovered at limited stage. It has benefited less from therapeutic advances than non-small cell lung cancer (NSCLC). The different steps and modalities of its management are well defined and codified. They involve a comprehensive staging assessment using CT scans of the chest, abdomen, and pelvis, PET-CT scans, and ideally brain imaging using MRI to avoid missing a more extensive stage of the disease, which would significantly alter the treatment strategy. The treatment consists of a combination of chemotherapy with platinum/ etoposide and radiotherapy, possibly delivered in a hyperfractionated schedule with two daily sessions followed by immunotherapy. SCLC is particularly both chemosensitive and radiosensitive, so that the initial evaluation shows frequently a complete response, and prophylactic cranial irradiation (PCI) is then recommended. Even if hyperfractionated accelerated radiotherapy (HFART) at the dose of 45Gy in 30 fractions has given the best results, most clinicians use once-daily chemoradiation regimen (60-70Gy). Studies have evaluated dose escalation either with HFRAT or with conventional fractionation (66 to 70Gy). Several trials are currently investigating the addition of immunotherapy to chemoradiation, hippocampus sparing PCI or the omission of PCI.

有限期小细胞肺癌（LS-SCLC）占所有肺癌的10-15%，由于其快速的肿瘤动力学，不到三分之一的SCLC在有限期被发现。与非小细胞肺癌（NSCLC）相比，它从治疗进展中获益较少。其管理的不同步骤和方式得到了很好的界定和编纂。它们包括使用胸部、腹部和骨盆的CT扫描进行全面的分期评估，PET-CT扫描，理想情况下使用MRI进行脑成像，以避免错过疾病的更广泛阶段，这将显著改变治疗策略。治疗包括化疗与铂/依托泊苷和放疗的组合，可能以每天两次的高分割时间表进行，然后进行免疫治疗。SCLC特别具有化学敏感性和放射敏感性，因此初步评估通常显示完全缓解，然后推荐预防性颅脑照射（PCI）。即使30次45Gy剂量的超分割加速放疗（hart）效果最好，大多数临床医生还是使用每日一次的放化疗方案（60-70Gy）。研究评估了HFRAT或常规分离（66至70Gy）的剂量递增。目前有几项试验正在研究在放化疗的基础上增加免疫治疗、保留海马体PCI或不进行PCI。

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引用次数: 0

Place de l'immunothérapie dans les CBNPC de stade III non résécables 免疫治疗在III期非分离cnpc中的位置

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00068-0

E. Giroux Leprieur , M. Pérol , J. Khalifa

Treatment of unresectable stage III non-small cell lung cancer is currently based on a combination of chemotherapy and radiotherapy, ideally concurrent, followed by consolidation with durvalumab administered for 1 year. Although this new therapeutic standard illustrates the technical progress of thoracic irradiation and the positive impact of anti-PD-L1 in the context of locally advanced disease, the results (progression-free survival of 34% at 5 years and overall survival of 43% at 5 years, no survival benefit in the absence of PD-L1 expression or in case of EGFR mutation) underline the need for further therapeutic improvement. This could involve optimizing strategies for combining immunotherapy with chemoradiotherapy, redefining the parameters of thoracic radiotherapy to promote synergy with immunotherapy, and integrating targeted therapies into the therapeutic strategy in cases of oncogenic addiction.

不可切除的III期非小细胞肺癌的治疗目前是基于化疗和放疗的联合治疗，理想情况下是同时进行，然后用durvalumab治疗1年。尽管这一新的治疗标准说明了胸部放疗的技术进步和抗PD-L1在局部晚期疾病背景下的积极影响，但结果（5年无进展生存率为34%，5年总生存率为43%，没有PD-L1表达或EGFR突变的情况下没有生存获益）强调了进一步改善治疗的必要性。这可能包括优化免疫治疗与放化疗结合的策略，重新定义胸部放疗的参数以促进与免疫治疗的协同作用，以及将靶向治疗纳入肿瘤成瘾病例的治疗策略。

引用次数: 0

Le dépistage du cancer du poumon 肺癌筛查

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00062-X

S. Couraud , E. Grolleau , B. Milleron , V. Gounant , O. Leleu

Several randomized trials have demonstrated that a low-dose thoracic CT scan screening strategy without contrast injection reduces both lung cancer mortality and overall mortality in a high-risk population. In France and Europe, several scientific societies have advocated for this screening to be performed in eligible individuals. In France, the eligibility criteria are: age between 50 and 75 years, a smoking history of more than 20 pack-years, either current smokers or those who have quit within the last 15 years. The IMPULSION national pilot study will begin in 2025 in 5 regions and in the whole territory in 2026.

几项随机试验表明，不注射造影剂的低剂量胸部CT扫描筛查策略可以降低高危人群的肺癌死亡率和总死亡率。在法国和欧洲，一些科学协会主张在符合条件的个体中进行这种筛查。在法国，资格标准是：年龄在50至75岁之间，吸烟史超过20包年，目前吸烟者或在过去15年内戒烟的人。impulse国家试点研究将于2025年在5个地区开始，并于2026年在全国范围内开展。

引用次数: 0

Populations particulières : Patients de Performance Status 2 et plus 特定人群：患者表现不佳2及以上

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00091-6

V. Gounant , L. Alvarez , Y.M. Xu , C. Mehlman , L. Nicolas , S. Guillerm , P. Mordant , G. Zalcman

Performance status (PS) is a measure of the patient's overall condition. Karnofsky and ECOG (Eastern Cooperative Oncology Group) are the most widely used scales. A three-point conversion scale allows a strong correlation between both scores: ECOG 0-1 = Karnofsky 100-80%, ECOG 2 = Karnofsky 60-70%, ECOG 3-4 = Karnofsky 50-10%. Numerous factors, whether linked to cancer or to comorbidities, can affect PS. PS remains a major independent prognostic factor in NSCLC (non small cell lung cancer) and SCLC (small cell lung cancer), despite its flawed reproducibility and the heterogeneity of cancer patients with poor PS. As a matter of fact, PS should be regarded as a stratification factor in research. All guidelines take PS into account as a therapeutic decision making tool, especially in the case of chemotherapy for metastatic NSCLC. Targeted therapy should be considered in case of metastatic disease with molecular targets regardless of PS, for its high effectiveness and good safety profile. Data regarding immunotherapy are rather sketchy. Tolerance seems to be fine. Findings regarding efficacy warrant careful selection of patients who might benefit from this therapy. In light of the European Medicines Agency call, let us build studies dedicated to patients as frail as they come and enroll them in clinical trials in such a way that they benefit, among others, from therapeutic advances. In order to apply clinical research findings to the general population, specific groups of patients should be more involved.

表现状态（Performance status， PS）是衡量患者整体状况的指标。Karnofsky和ECOG （Eastern Cooperative Oncology Group）是使用最广泛的量表。三分转换量表允许两个分数之间的强相关性：ECOG 0-1 = Karnofsky 100-80%, ECOG 2 = Karnofsky 60-70%, ECOG 3-4 = Karnofsky 50-10%。影响PS的因素很多，无论是与癌症相关还是与合并症相关。尽管PS在非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）中存在可重复性缺陷，且PS差的癌症患者存在异质性，但仍是一个主要的独立预后因素。事实上，在研究中，PS应被视为一个分层因素。所有指南都将PS作为治疗决策工具，特别是在转移性非小细胞肺癌化疗的情况下。对于转移性疾病的分子靶点，无论PS如何，都应考虑靶向治疗，因为它具有高有效性和良好的安全性。关于免疫治疗的数据相当粗略。宽容似乎很好。关于疗效的发现需要仔细选择可能从这种治疗中受益的患者。根据欧洲药品管理局（European Medicines Agency）的呼吁，让我们建立专门针对身体虚弱的病人的研究，让他们参加临床试验，让他们从治疗进步中受益。为了将临床研究成果应用于一般人群，应该更多地参与特定患者群体。

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引用次数: 0

Algorithme thérapeutique en 2025 des cancers bronchiques non à petites cellules avec mutation de l'EGFR 2025年EGFR突变非小细胞肺癌的治疗算法

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00076-X

M. Ferreira , V. Fallet , S. Baldacci , A.B. Cortot , J. Cadranel

EGFR mutations remain the most frequently observed targetable oncogenic driver in non-small cell lung cancer (NSCLC), accounting for 12% of adenocarcinomas and 44% of NSCLC cases in non-smokers in France. The «common» EGFR mutations—exon 19 deletions and the exon 21 L858R mutation—are found in 89% of cases. The use of new molecular biology techniques has led to the identification of «rare» EGFR mutations, particularly exon 20 insertions, and has also revealed molecular heterogeneity both at diagnosis and during follow-up. This heterogeneity partly explains the variability in the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) and contributes to the emergence of resistant clones. Osimertinib has been the standard first-line therapy for several years. However, the role of combined chemotherapy and the emergence of amivantamab—a bispecific EGFR-MET antibody—are changing the landscape of first-line treatment options, whether in combination or not, as well as the sequencing of therapies, with the goal of improving overall survival.

These advances, however, come with increased toxicities and a risk of impaired quality of life, underscoring the need to carefully select patients who are most likely to benefit from each therapeutic option. Finally, the indications for osimertinib are expanding, with its use now approved in the adjuvant post-surgical setting and its anticipated arrival in neoadjuvant (pre-operative) and consolidation therapy after chemoradiation for patients with localized or locally advanced unresectable NSCLC.

EGFR突变仍然是非小细胞肺癌（NSCLC）中最常见的可靶向致癌驱动因素，在法国非吸烟者中占12%的腺癌和44%的NSCLC病例。“常见的”EGFR突变——外显子19缺失和外显子21 L858R突变——在89%的病例中被发现。新的分子生物学技术的使用已经导致了“罕见”EGFR突变的鉴定，特别是外显子20插入，并且还揭示了诊断和随访期间的分子异质性。这种异质性部分解释了EGFR酪氨酸激酶抑制剂（EGFR- tkis）疗效的可变性，并有助于耐药克隆的出现。多年来，奥西替尼一直是标准的一线治疗方法。然而，联合化疗的作用和amivantamab（双特异性EGFR-MET抗体）的出现正在改变一线治疗方案的格局，无论联合与否，以及治疗的顺序，目标是提高总生存率。然而，这些进步伴随着毒性的增加和生活质量受损的风险，强调需要仔细选择最有可能从每种治疗方案中受益的患者。最后，奥希替尼的适应症正在扩大，目前已被批准用于辅助术后治疗，并有望用于局部或局部晚期不可切除的NSCLC患者放化疗后的新辅助（术前）和巩固治疗。

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引用次数: 0

Algorithme thérapeutique des cancers bronchiques non à petites cellules avec fusion ALK, ROSI et RET ALK、ROSI、RET融合治疗非小细胞肺癌的算法

Q4 Medicine

Revue des Maladies Respiratoires Actualites

Pub Date : 2025-10-01 DOI: 10.1016/S1877-1203(25)00077-1

A. Swalduz , A. Cortot , M. Duruisseaux

ALK (3-7%), ROS1 (1-2%), and RET (1-2%) rearrangements differ epidemiologically from other non-small cell lung cancers. They are more frequently observed in younger patients, light or never smokers, and are predominantly associated with adenocarcinoma histology. Several fusion partners have been identified for each of these genes, with some partners shared across targets. Identifying these genomic alterations at the time of initial diagnosis in advanced non-small cell lung cancer patients is essential to guide first-line treatment decisions, direct patients toward effective targeted therapies, and avoid ineffective strategies such as immune checkpoint inhibitors in monotherapy or potentially toxic treatment sequences. In patients with ALK rearrangements, lorlatinib is the first-line standard, with a 5-year progression-free survival (PFS) rate of 60% and remarkable intracranial efficacy. Post-lorlatinib resistance mechanisms in first-line therapy appear to be ALK-independent, and chemotherapy currently remains the standard second-line option. In patients previously treated with brigatinib or alectinib, secondline therapy should be guided by the identification of resistance mechanisms. Neladalkib, a fourth-generation ALK inhibitor, is currently available through an early access program. For ROSI-rearranged non-small cell lung cancers, crizotinib is the only approved targeted therapy to date, although agents such as taletrectinib and zidesamtinib (also available through early access) show promising activity. Finally, for RET-rearranged non-small cell lung cancers, selpercatinib is now the standard of care from the first-line setting, offering significant clinical benefit.

ALK（3-7%）、ROS1（1-2%）和RET（1-2%）重排在流行病学上与其他非小细胞肺癌不同。它们更常见于年轻患者，轻度或从不吸烟，并且主要与腺癌组织学相关。这些基因的几个融合伴侣已经被确定，其中一些伴侣在目标中共享。在晚期非小细胞肺癌患者的初始诊断时识别这些基因组改变对于指导一线治疗决策，指导患者进行有效的靶向治疗，避免无效的策略，如单药治疗中的免疫检查点抑制剂或潜在毒性治疗序列至关重要。在ALK重排患者中，lorlatinib是一线标准，5年无进展生存（PFS）率为60%，颅内疗效显著。一线治疗的氯拉替尼耐药机制似乎与alk无关，化疗目前仍是标准的二线选择。在先前接受布加替尼或阿勒替尼治疗的患者中，二线治疗应以确定耐药机制为指导。Neladalkib是第四代ALK抑制剂，目前通过早期准入项目可获得。对于rossi重排的非小细胞肺癌，尽管taletrectinib和zidesamtinib（也可通过早期获得）等药物显示出有希望的活性，但迄今为止，克唑替尼是唯一被批准的靶向治疗药物。最后，对于ret重排的非小细胞肺癌，selpercatinib现在是从一线开始的标准治疗，提供了显着的临床益处。

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