Pub Date : 2025-10-01DOI: 10.1016/S1877-1203(25)00078-3
A. Chour , C. Lafitte , M. Boussageon , T. Pierret , M. Duruisseaux
The KRASG12C mutation represents the most common genomic alteration in lung adenocarcinomas in non-Asian populations. This genomic alteration leads to constitutive activation of the KRASG12C protein, stimulating signaling cascades involved in proliferation and malignant transformation. Historically considered an undruggable therapeutic target, this mutation has now become actionable through the development of sotorasib and adagrasib, selective inhibitors of KRASG12C in its inactive state. This literature review examines the biology of KRAS mutations, details the mechanisms of action of novel KRASG12C inhibitors along with their clinical benefit, safety profile, associated resistance mechanisms, and development perspectives.
{"title":"Prise en charge du cancer pulmonaire non à petites cellules avec mutation de KRAS","authors":"A. Chour , C. Lafitte , M. Boussageon , T. Pierret , M. Duruisseaux","doi":"10.1016/S1877-1203(25)00078-3","DOIUrl":"10.1016/S1877-1203(25)00078-3","url":null,"abstract":"<div><div>The <em>KRAS<sup>G12C</sup></em> mutation represents the most common genomic alteration in lung adenocarcinomas in non-Asian populations. This genomic alteration leads to constitutive activation of the KRASG12C protein, stimulating signaling cascades involved in proliferation and malignant transformation. Historically considered an undruggable therapeutic target, this mutation has now become actionable through the development of sotorasib and adagrasib, selective inhibitors of KRASG12C in its inactive state. This literature review examines the biology of KRAS mutations, details the mechanisms of action of novel KRASG12C inhibitors along with their clinical benefit, safety profile, associated resistance mechanisms, and development perspectives.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S221-2S229"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/S1877-1203(25)00055-2
J.-C. Pairon , L. Boudet , F. Delva , P. Andujar
In France, lung cancer is the 3rd most common cancer (52,777 new cases in 2023) and the 1st cause of cancer-related death (30,896 cases in 2022). While incidence and mortality rates in men have stabilized, they are demonstrating an alarming growth in women, linked to the increase in female tobacco consumption. Combined, close to 90 % of lung cancer cases are attributable to modifiable factors, offering numerous levers for prevention policies. While tobacco smoking is indeed the main risk factor for lung cancer (attributable fraction: higher than 80 %), the risk factors and exposures are numerous, such as a diet low in fruit (10%), occupational exposures (16%), and environmental exposures, such as radon (10%) and outdoor air pollution (3.6 %). In 2025, the International Agency for Research on Cancer identified 31 definite carcinogenic agents and carcinogenic exposure situations from occupational or environmental sources, for which there is sufficient evidence of an excess of lung cancer in humans. In the clinical management of patients, it is important to identify any occupational exposure to carcinogenic agents. Recognition of lung cancer as an occupational disease is a major medical and social issue for patients. Several approaches can be used to identify exposure to occupational carcinogens: occupational interview (with specific questionnaires or self-questionnaires), biometrological analysis for certain agents, or imaging (for asbestos and crystalline silica). Once an occupational exposure has been identified, the clinician may or may not advise the patient to file an occupational disease claim.
{"title":"Épidémiologie et facteurs de risques professionnels et environnementaux du cancer bronchopulmonaire","authors":"J.-C. Pairon , L. Boudet , F. Delva , P. Andujar","doi":"10.1016/S1877-1203(25)00055-2","DOIUrl":"10.1016/S1877-1203(25)00055-2","url":null,"abstract":"<div><div>In France, lung cancer is the 3rd most common cancer (52,777 new cases in 2023) and the 1st cause of cancer-related death (30,896 cases in 2022). While incidence and mortality rates in men have stabilized, they are demonstrating an alarming growth in women, linked to the increase in female tobacco consumption. Combined, close to 90 % of lung cancer cases are attributable to modifiable factors, offering numerous levers for prevention policies. While tobacco smoking is indeed the main risk factor for lung cancer (attributable fraction: higher than 80 %), the risk factors and exposures are numerous, such as a diet low in fruit (10%), occupational exposures (16%), and environmental exposures, such as radon (10%) and outdoor air pollution (3.6 %). In 2025, the International Agency for Research on Cancer identified 31 definite carcinogenic agents and carcinogenic exposure situations from occupational or environmental sources, for which there is sufficient evidence of an excess of lung cancer in humans. In the clinical management of patients, it is important to identify any occupational exposure to carcinogenic agents. Recognition of lung cancer as an occupational disease is a major medical and social issue for patients. Several approaches can be used to identify exposure to occupational carcinogens: occupational interview (with specific questionnaires or self-questionnaires), biometrological analysis for certain agents, or imaging (for asbestos and crystalline silica). Once an occupational exposure has been identified, the clinician may or may not advise the patient to file an occupational disease claim.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S8-2S14"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/S1877-1203(25)00086-2
T. Pierret , M. Duruisseaux , C. Lafitte , M. Boussageon , L. Chalabreysse , J.-M. Maury , M. Le Bon , B. Besse , N. Girard
Thymic epithelial tumors are rare malignancies, that may be aggressive and difficult to treat, with variable prognosis. The histopathological classification distinguishes two major tumor types: thymomas and thymic carcinomas. Autoimmune manifestations are observed in nearly one third of patients at diagnosis; myasthenia gravis is the most common, followed by pure red cell aplasia and hypogammaglobulinemia. The historical staging system is the Masaoka system, reviewed by Koga; the 9th TNM system is standard since 2025. Assessment of resectability is the first step in the treatment of a thymic tumour, even at an advanced stage; even in advanced cases, complete resection remains the most significant prognostic factor for patient survival. If complete resection seems possible from the outset, surgery is the first stage of treatment, possibly supplemented by postoperative radiotherapy. In the case of unresectable thymic tumours, a pre-therapeutic biopsy should be performed for diagnostic purposes. The treatment strategy is based on induction chemotherapy followed by surgical resection or irradiation. Patients who remain ineligible for focal treatment receive chemotherapy exclusively. More targeted therapies would appear to be of interest as a subsequent line of treatment, as would immunotherapy in the context of thymic carcinoma, although toxicity needs to be monitored very regularly. Following an INCa call for tenders in 2010, a national care network of expert centres for thymoma and thymic carcinoma was set up in 2012: the RYTHMIC network (Thymic Tumours and Cancer Network). This network provides answers to very specific diagnostic or therapeutic questions in the context of rare tumours, as well as collating information on treatment to help improve it in the future.
{"title":"Les tumeurs thymiques : traitements systémiques et place de la radiothérapie","authors":"T. Pierret , M. Duruisseaux , C. Lafitte , M. Boussageon , L. Chalabreysse , J.-M. Maury , M. Le Bon , B. Besse , N. Girard","doi":"10.1016/S1877-1203(25)00086-2","DOIUrl":"10.1016/S1877-1203(25)00086-2","url":null,"abstract":"<div><div>Thymic epithelial tumors are rare malignancies, that may be aggressive and difficult to treat, with variable prognosis. The histopathological classification distinguishes two major tumor types: thymomas and thymic carcinomas. Autoimmune manifestations are observed in nearly one third of patients at diagnosis; myasthenia gravis is the most common, followed by pure red cell aplasia and hypogammaglobulinemia. The historical staging system is the Masaoka system, reviewed by Koga; the 9th TNM system is standard since 2025. Assessment of resectability is the first step in the treatment of a thymic tumour, even at an advanced stage; even in advanced cases, complete resection remains the most significant prognostic factor for patient survival. If complete resection seems possible from the outset, surgery is the first stage of treatment, possibly supplemented by postoperative radiotherapy. In the case of unresectable thymic tumours, a pre-therapeutic biopsy should be performed for diagnostic purposes. The treatment strategy is based on induction chemotherapy followed by surgical resection or irradiation. Patients who remain ineligible for focal treatment receive chemotherapy exclusively. More targeted therapies would appear to be of interest as a subsequent line of treatment, as would immunotherapy in the context of thymic carcinoma, although toxicity needs to be monitored very regularly. Following an INCa call for tenders in 2010, a national care network of expert centres for thymoma and thymic carcinoma was set up in 2012: the RYTHMIC network (Thymic Tumours and Cancer Network). This network provides answers to very specific diagnostic or therapeutic questions in the context of rare tumours, as well as collating information on treatment to help improve it in the future.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S286-2S293"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/S1877-1203(25)00085-0
G. Drevet , E. Gagnepain , L. Chalabreyse , C. Lafite , T. Pierret , J.-M. Maury
Thymic epithelial tumors (TETs) belong to rare orphan disease, nevertheless, they represent the most frequent anterior mediastinum tumors. Two distinguables entities are identified by the WHO classification: (1) thymomas, respecting the normal architecture of the gland and composed by tumoral epithelial cells associated with normal lymphocytes and (2) thymic carcinomas. TETS are frequently associated, in 30%, with paraneoplastic syndrome's, including in most of cases myasthenia gravis with anti acetylcholin receptor antibodies (RACH).The Masaoka-Koga classification, ITMIG modified in 2012 governs the principles of treatment. A multidisciplinary approach including thoracic oncologist, radiotherapist and thoracic surgeons is the standard of care and complex cases must be discussed in the French national network (RYTHMIC, thymic tumors and cancers, INCa labialized in 2012) within expert centers. The evident principle of care includes: a close evaluation of resectability, when feasible a surgical resection R0 (corner stone of a multimodal standard of care) non/or associated with neoadjuvant or adjuvant chemotherapies (CAP and carbo-taxol based) and radiotherapy.
{"title":"Tumeurs thymiques : prise en charge chirurgicale","authors":"G. Drevet , E. Gagnepain , L. Chalabreyse , C. Lafite , T. Pierret , J.-M. Maury","doi":"10.1016/S1877-1203(25)00085-0","DOIUrl":"10.1016/S1877-1203(25)00085-0","url":null,"abstract":"<div><div>Thymic epithelial tumors (TETs) belong to rare orphan disease, nevertheless, they represent the most frequent anterior mediastinum tumors. Two distinguables entities are identified by the WHO classification: (1) thymomas, respecting the normal architecture of the gland and composed by tumoral epithelial cells associated with normal lymphocytes and (2) thymic carcinomas. TETS are frequently associated, in 30%, with paraneoplastic syndrome's, including in most of cases myasthenia gravis with anti acetylcholin receptor antibodies (RACH).The Masaoka-Koga classification, ITMIG modified in 2012 governs the principles of treatment. A multidisciplinary approach including thoracic oncologist, radiotherapist and thoracic surgeons is the standard of care and complex cases must be discussed in the French national network (RYTHMIC, thymic tumors and cancers, INCa labialized in 2012) within expert centers. The evident principle of care includes: a close evaluation of resectability, when feasible a surgical resection R0 (corner stone of a multimodal standard of care) non/or associated with neoadjuvant or adjuvant chemotherapies (CAP and carbo-taxol based) and radiotherapy.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S279-2S285"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/S1877-1203(25)00066-7
J. Slomka , G. Eberst , V. Westeel , M. Wislez
Surgical resection is the cornerstone of the management of resectable stage I to III nonsmall cell lung cancer (NSCLC). Platinum-based chemotherapy, whether neoadjuvant or adjuvant, has long been combined with surgery for patients with resectable stage II-III disease, although the benefits are modest, with an overall survival gain of approximately 5 %. Recently, immunotherapy has been incorporated into neoadjuvant, adjuvant, and perioperative treatment regimens based on data showing improvements in event-free survival (EFS), disease-free survival (DFS), and overall survival in patients with localized or locally advanced, resectable NSCLC without oncogenic driver mutations. Two phase 3 trials demonstrated a benefit of adjuvant immunotherapy, leading to European approval, although these are not currently reimbursed in France. Six phase 3 trials CheckMate-816, AEGEAN, CheckMate-77T, NeoTORCH, KEYNOTE-671, and RATIONALE-315 have shown a benefit from adding an immune checkpoint inhibitor to chemotherapy in the neoadjuvant or perioperative setting. Based on the results of CheckMate-816, neoadjuvant nivolumab has been approved in combination with platinum-based chemotherapy for adult patients with resectable NSCLC at high risk of recurrence, whose tumors express PD-L1 > 1 % and are negative for EGFR mutations and ALK rearrangements.
{"title":"L'immunothérapie péri-opératoire des cancers bronchiques non à petites cellules (CBNPC) : standards actuels et perspectives","authors":"J. Slomka , G. Eberst , V. Westeel , M. Wislez","doi":"10.1016/S1877-1203(25)00066-7","DOIUrl":"10.1016/S1877-1203(25)00066-7","url":null,"abstract":"<div><div>Surgical resection is the cornerstone of the management of resectable stage I to III nonsmall cell lung cancer (NSCLC). Platinum-based chemotherapy, whether neoadjuvant or adjuvant, has long been combined with surgery for patients with resectable stage II-III disease, although the benefits are modest, with an overall survival gain of approximately 5 %. Recently, immunotherapy has been incorporated into neoadjuvant, adjuvant, and perioperative treatment regimens based on data showing improvements in event-free survival (EFS), disease-free survival (DFS), and overall survival in patients with localized or locally advanced, resectable NSCLC without oncogenic driver mutations. Two phase 3 trials demonstrated a benefit of adjuvant immunotherapy, leading to European approval, although these are not currently reimbursed in France. Six phase 3 trials CheckMate-816, AEGEAN, CheckMate-77T, NeoTORCH, KEYNOTE-671, and RATIONALE-315 have shown a benefit from adding an immune checkpoint inhibitor to chemotherapy in the neoadjuvant or perioperative setting. Based on the results of CheckMate-816, neoadjuvant nivolumab has been approved in combination with platinum-based chemotherapy for adult patients with resectable NSCLC at high risk of recurrence, whose tumors express PD-L1 > 1 % and are negative for <em>EGFR</em> mutations and <em>ALK</em> rearrangements.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S98-2S105"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/S1877-1203(25)00071-0
C. Le Péchoux , A. Mavrikios , A. Botticella , D. Lavigne , A. Camps-Malea , P. Abdayem , P. Lavaud , M. Frelaut , C. Parisi , J. Remon-Masip , A. Levy
In patients with oligometastatic NSCLC (less than 5 metastatic sites in 3 or fewer organs), treatment is based on systemic therapy chosen according to the anatomopathological result and the molecular profile. Randomized studies have shown that adding local ablative treatment to systemic treatment can improve the outcome of these patients. Radiotherapy, and more specifically stereotactic radiotherapy (SRT), has been the most studied LAT. The systemic treatments most frequently associated with SRT are targeted therapies in patients with NSCLC with driver mutation and immunotherapy in the majority of patients with NSCLC without any driver mutation. Systemic treatment is most often continued, sometimes interrupted briefly depending on the molecule. Thus, SRT is often administered in less than 5 sessions, at a variable total dose. The decision should be individualized and validated in a multidisciplinary meeting. Ideally such patients should be included in trials.
{"title":"Comment irradier un patient sous traitement systémique (thérapie ciblée, immunothérapie, ADC) ?","authors":"C. Le Péchoux , A. Mavrikios , A. Botticella , D. Lavigne , A. Camps-Malea , P. Abdayem , P. Lavaud , M. Frelaut , C. Parisi , J. Remon-Masip , A. Levy","doi":"10.1016/S1877-1203(25)00071-0","DOIUrl":"10.1016/S1877-1203(25)00071-0","url":null,"abstract":"<div><div>In patients with oligometastatic NSCLC (less than 5 metastatic sites in 3 or fewer organs), treatment is based on systemic therapy chosen according to the anatomopathological result and the molecular profile. Randomized studies have shown that adding local ablative treatment to systemic treatment can improve the outcome of these patients. Radiotherapy, and more specifically stereotactic radiotherapy (SRT), has been the most studied LAT. The systemic treatments most frequently associated with SRT are targeted therapies in patients with NSCLC with driver mutation and immunotherapy in the majority of patients with NSCLC without any driver mutation. Systemic treatment is most often continued, sometimes interrupted briefly depending on the molecule. Thus, SRT is often administered in less than 5 sessions, at a variable total dose. The decision should be individualized and validated in a multidisciplinary meeting. Ideally such patients should be included in trials.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S143-2S150"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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