Pub Date : 2025-10-01DOI: 10.1016/S1877-1203(25)00056-4
C. Ricordel , C. Pierre , Y. Le Guen , H. Lena
Non-small cell lung cancer represents the most prevalent form of lung cancer. Its biological understanding is currently framed by two principal models: the multistep model, which involves the progressive accumulation of genetic alterations often associated with tobacco exposure, and the oncogene addiction model, in which tumor growth is critically dependent on a single genetic driver. Advances in genomics have enabled more precise identification of mutations underlying tumor initiation and progression, as well as factors shaping therapeutic response. Certain precancerous lesions may progress to invasive disease through specific genetic events, modulation of the immune microenvironment, or external influences such as pollution. Emerging evidence indicates that pollutants can promote the emergence or activation of pre-existing tumor clones via inflammatory pathways. The oncogene addiction paradigm has facilitated the development of effective targeted therapies for defined patient subgroups, although therapeutic efficacy is frequently limited by mechanisms of resistance. Large-scale sequencing studies have further revealed the pronounced heterogeneity of lung tumors, characterized by complex clonal evolution shaped by treatment pressure, immune surveillance, and environmental factors. This heterogeneity likely underlies both intrinsic and acquired resistance to targeted agents. Within the framework of precision medicine, these insights provide a foundation for optimizing therapeutic strategies and may inform the development of novel approaches to prevention and longitudinal disease monitoring.
{"title":"Oncogenèse pulmonaire : fondements moléculaires et implications thérapeutiques","authors":"C. Ricordel , C. Pierre , Y. Le Guen , H. Lena","doi":"10.1016/S1877-1203(25)00056-4","DOIUrl":"10.1016/S1877-1203(25)00056-4","url":null,"abstract":"<div><div>Non-small cell lung cancer represents the most prevalent form of lung cancer. Its biological understanding is currently framed by two principal models: the multistep model, which involves the progressive accumulation of genetic alterations often associated with tobacco exposure, and the oncogene addiction model, in which tumor growth is critically dependent on a single genetic driver. Advances in genomics have enabled more precise identification of mutations underlying tumor initiation and progression, as well as factors shaping therapeutic response. Certain precancerous lesions may progress to invasive disease through specific genetic events, modulation of the immune microenvironment, or external influences such as pollution. Emerging evidence indicates that pollutants can promote the emergence or activation of pre-existing tumor clones via inflammatory pathways. The oncogene addiction paradigm has facilitated the development of effective targeted therapies for defined patient subgroups, although therapeutic efficacy is frequently limited by mechanisms of resistance. Large-scale sequencing studies have further revealed the pronounced heterogeneity of lung tumors, characterized by complex clonal evolution shaped by treatment pressure, immune surveillance, and environmental factors. This heterogeneity likely underlies both intrinsic and acquired resistance to targeted agents. Within the framework of precision medicine, these insights provide a foundation for optimizing therapeutic strategies and may inform the development of novel approaches to prevention and longitudinal disease monitoring.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S15-2S24"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236483","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)00059-X
C. Leonce , F. Escande , K. Leroy , C. Mascaux , C. Descarpentries , O. Farchi , H. Blons , M. Beau-Faller
The identification of targetable molecular alterations is now required before starting any treatment in patients with non-small cell lung cancer. Molecular diagnosis is mainly realized on tissue samples but circulating tumor DNA analysis has also become a valuable tool in the daily practice. In recent years, the diversification of therapeutic targets has been a real challenge in terms of detection and requires the use of various molecular biology techniques adapted to assess targets on DNA (point mutations, small deletions/insertions, gene amplification) but also on RNA (fusion transcript). The choice of the technology is directed by the clinical context, the exhaustiveness of the results, the analytical sensitivity, the delay of results and cost. For this, a close discussion with clinicians and pathologists is essential.
{"title":"Cancer du poumon : quel bilan de biologie moléculaire ?","authors":"C. Leonce , F. Escande , K. Leroy , C. Mascaux , C. Descarpentries , O. Farchi , H. Blons , M. Beau-Faller","doi":"10.1016/S1877-1203(25)00059-X","DOIUrl":"10.1016/S1877-1203(25)00059-X","url":null,"abstract":"<div><div>The identification of targetable molecular alterations is now required before starting any treatment in patients with non-small cell lung cancer. Molecular diagnosis is mainly realized on tissue samples but circulating tumor DNA analysis has also become a valuable tool in the daily practice. In recent years, the diversification of therapeutic targets has been a real challenge in terms of detection and requires the use of various molecular biology techniques adapted to assess targets on DNA (point mutations, small deletions/insertions, gene amplification) but also on RNA (fusion transcript). The choice of the technology is directed by the clinical context, the exhaustiveness of the results, the analytical sensitivity, the delay of results and cost. For this, a close discussion with clinicians and pathologists is essential.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S38-2S45"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236486","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)00080-1
S. Lantuejoul , F. Forest , F. Damiola , D. Moro-Sibilot , L. Falchero
Pulmonary neuroendocrine neoplasms (NENs) have been classified since the 2021 WHO classification as neuroendocrine tumors (NETs), including typical low-grade G1 carcinoids (CT) and atypical intermediate-grade G2 carcinoids (CA), and high-grade malignant neuroendocrine carcinomas (NEC), including large cell neuroendocrine carcinomas (LCNEC) and small cell carcinomas (SCLC). The diagnostic criteria adopted in 2021 for all NETs remain similar to those used in the 1999 WHO classification. However, recent histomolecular data enabled to better characterize a new entity, Grade 3 NET, with NET morphology but a mitotic count and Ki67 proliferation index of LCNEC, and NETs with a poor prognosis with genomics similar to LCNEC or “supra-carcinoids.” There are also two histomolecular groups of LCNEC whose therapeutic management differs according to their genomic profile, as well as different variants of SCLC identified based on their transcriptomic expression profile, with diagnostic and probably therapeutic implications in the future.
{"title":"Classification des néoplasmes neuroendocrines pulmonaires et impacts sur la pratique clinique","authors":"S. Lantuejoul , F. Forest , F. Damiola , D. Moro-Sibilot , L. Falchero","doi":"10.1016/S1877-1203(25)00080-1","DOIUrl":"10.1016/S1877-1203(25)00080-1","url":null,"abstract":"<div><div>Pulmonary neuroendocrine neoplasms (NENs) have been classified since the 2021 WHO classification as neuroendocrine tumors (NETs), including typical low-grade G1 carcinoids (CT) and atypical intermediate-grade G2 carcinoids (CA), and high-grade malignant neuroendocrine carcinomas (NEC), including large cell neuroendocrine carcinomas (LCNEC) and small cell carcinomas (SCLC). The diagnostic criteria adopted in 2021 for all NETs remain similar to those used in the 1999 WHO classification. However, recent histomolecular data enabled to better characterize a new entity, Grade 3 NET, with NET morphology but a mitotic count and Ki67 proliferation index of LCNEC, and NETs with a poor prognosis with genomics similar to LCNEC or “supra-carcinoids.” There are also two histomolecular groups of LCNEC whose therapeutic management differs according to their genomic profile, as well as different variants of SCLC identified based on their transcriptomic expression profile, with diagnostic and probably therapeutic implications in the future.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S237-2S244"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236601","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)00070-9
L. Bigay-Game , L. Alvarez , A. Rabeau , V. Gounant , C. Daigmorte , C. Mehlman , C. Joseph , Y.M. Xu , J.E. Simon , G. Zalcman
The oligo-metastatic disease concept refers to a tumor type having a limited ability for metastazing, with the still speculative idea that loco-regional treatments could be curative in a subset of patients with oligo-metastases. It would imply an intermediary state between a cancer tumor with diffuse metastatic effusion and a tumor purely localized to the primitive organ (i.e. the lung), that is to say a cancer disease with a limited number of metastatic sites, the definition according to different authors, ranging from 1 to 5 metastases, most often in no more than 1 to 2 organs. Such concepts emerged from mainly retrospective studies, regional or national databases, or meta-analyses, most of them before the targeted therapies and modern immunotherapy eras, suggesting that adding locoregional treatments (surgery, radiotherapy, thermos-ablation, radio-frequence) to systemic treatments would increase survival, although all those studies are debatable, because of their retrospective design. Prospective trials are still rare, essentially with phase 2 trials, often accruing patients with different cancer and organ types, with modest sample size of patients with NSCLC, limiting their meaning. Because of the unprecedently observed efficacy of new systemic targeted therapies and immunotherapy in NSCLC, new concepts also emerged such as oligo-progression, oligo-persistence or residual tumor disease, although previously described for other tumor types. The current review aims to precise some complex and sometimes contradictory definitions, to synthetize the results of the main retrospective studies and meta-analyses, to examine the rare prospective studies and decipher the current situation cases that could occur. Actually, the medical reasoning differs according to the addictive mutational tumor status with efficient available targeted therapy, or in patients without addictive mutation, according to immuno-or immunochemotherapy response, or according to the timepoint, at diagnosis, during treatment, or after the two years of immunotherapy, all these different situations leading to possibly different approaches, the evidence from literature being still fragmentary.
{"title":"Cancers bronchiques non à petites cellules oligo-métastatiques, oligo-persistance, oligo-progression, maladie résiduelle : de quoi parle-t-on ? Quelle prise en charge ?","authors":"L. Bigay-Game , L. Alvarez , A. Rabeau , V. Gounant , C. Daigmorte , C. Mehlman , C. Joseph , Y.M. Xu , J.E. Simon , G. Zalcman","doi":"10.1016/S1877-1203(25)00070-9","DOIUrl":"10.1016/S1877-1203(25)00070-9","url":null,"abstract":"<div><div>The oligo-metastatic disease concept refers to a tumor type having a limited ability for metastazing, with the still speculative idea that loco-regional treatments could be curative in a subset of patients with oligo-metastases. It would imply an intermediary state between a cancer tumor with diffuse metastatic effusion and a tumor purely localized to the primitive organ (i.e. the lung), that is to say a cancer disease with a limited number of metastatic sites, the definition according to different authors, ranging from 1 to 5 metastases, most often in no more than 1 to 2 organs. Such concepts emerged from mainly retrospective studies, regional or national databases, or meta-analyses, most of them before the targeted therapies and modern immunotherapy eras, suggesting that adding locoregional treatments (surgery, radiotherapy, thermos-ablation, radio-frequence) to systemic treatments would increase survival, although all those studies are debatable, because of their retrospective design. Prospective trials are still rare, essentially with phase 2 trials, often accruing patients with different cancer and organ types, with modest sample size of patients with NSCLC, limiting their meaning. Because of the unprecedently observed efficacy of new systemic targeted therapies and immunotherapy in NSCLC, new concepts also emerged such as oligo-progression, oligo-persistence or residual tumor disease, although previously described for other tumor types. The current review aims to precise some complex and sometimes contradictory definitions, to synthetize the results of the main retrospective studies and meta-analyses, to examine the rare prospective studies and decipher the current situation cases that could occur. Actually, the medical reasoning differs according to the addictive mutational tumor status with efficient available targeted therapy, or in patients without addictive mutation, according to immuno-or immunochemotherapy response, or according to the timepoint, at diagnosis, during treatment, or after the two years of immunotherapy, all these different situations leading to possibly different approaches, the evidence from literature being still fragmentary.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S127-2S142"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236546","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)00084-9
M. Locatelli-Sanchez , A. Scherpereel , N. Venissac , S. Humez , L. Ulmer , S. Brosseau , X. Dhalluin , D. Nunes , V. Gounant , S. Lantuejoul , G. Zalcman
Pleural mesothelioma (PM) is a quite rare tumor, usually due to previous asbestos exposure. Its global prognosis is poor, without validated curative treatment to date. Diagnosis relies ideally on thoracoscopy with pleural biopsies, ± combined with (immediate) talc pleurodesis. Surgery with curative intent, included with multimodal treatment and restrained to highly selected patients, was recently rechallenged. As frontline treatment, standard pemetrexed/platinum-based chemotherapy was lightly improved by addition of bevacizumab. It is currently challenged by the immunotherapy combination of Nivolumab + Ipilimumab, and perhaps soon by combinations of chemotherapy + immunotherapy. No standard treatment is firmly validated beyond first line treatment, even if anti-PD-1/PD-L1 ± anti-CTLA-4 checkpoint inhibitors also exhibited some interesting results in this setting, in phase II and III clinical trials. Therefore, the search of new treatments, strategies and biomarkers is a crucial goal, and recruitment of patients in clinical trials strongly encouraged. Other immunotherapies alone or combined with standard treatments and/or targeted therapies, multimodal strategies are currently assessed. In France, the national network of expert centers for PM management, “NETMESO” (labelled by INCa), aims at proposing an optimal management to all patients systematically discussed in regional (± national) MTB dedicated to PM, and at stimulating clinical and translational research in collaboration with its partners including patients advocating associations.
{"title":"Mésothéliome pleural : algorithme thérapeutique","authors":"M. Locatelli-Sanchez , A. Scherpereel , N. Venissac , S. Humez , L. Ulmer , S. Brosseau , X. Dhalluin , D. Nunes , V. Gounant , S. Lantuejoul , G. Zalcman","doi":"10.1016/S1877-1203(25)00084-9","DOIUrl":"10.1016/S1877-1203(25)00084-9","url":null,"abstract":"<div><div>Pleural mesothelioma (PM) is a quite rare tumor, usually due to previous asbestos exposure. Its global prognosis is poor, without validated curative treatment to date. Diagnosis relies ideally on thoracoscopy with pleural biopsies, ± combined with (immediate) talc pleurodesis. Surgery with curative intent, included with multimodal treatment and restrained to highly selected patients, was recently rechallenged. As frontline treatment, standard pemetrexed/platinum-based chemotherapy was lightly improved by addition of bevacizumab. It is currently challenged by the immunotherapy combination of Nivolumab + Ipilimumab, and perhaps soon by combinations of chemotherapy + immunotherapy. No standard treatment is firmly validated beyond first line treatment, even if anti-PD-1/PD-L1 ± anti-CTLA-4 checkpoint inhibitors also exhibited some interesting results in this setting, in phase II and III clinical trials. Therefore, the search of new treatments, strategies and biomarkers is a crucial goal, and recruitment of patients in clinical trials strongly encouraged. Other immunotherapies alone or combined with standard treatments and/or targeted therapies, multimodal strategies are currently assessed. In France, the national network of expert centers for PM management, “NETMESO” (labelled by <em>INCa),</em> aims at proposing an optimal management to all patients systematically discussed in regional (± national) MTB dedicated to PM, and at stimulating clinical and translational research in collaboration with its partners including patients advocating associations.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S270-2S278"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236606","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)00065-5
E. Martin , F. Bonnet , M. Rakotosamimanana , C. Chevalier , J. Baude
Surgery remains the reference treatment for stage T1-T2 N0 primary non-small cell lung cancer (segmentectomy of lobectomy with lymph nodes dissection). For patients with surgical contraindication or refusing surgery, stereotactic radiotherapy is the standard alternative treatment allowing high local control rate and low toxicity for peripheral lesions. Some complex situations must be identified such as the presence of an interstitial lung fibrosis and the central location with the proximity of hollow organs (bronchi and esophagus), sensitive to high doses per fraction. The ultracentral location is particularly at risk of serious complications and should prompt a discussion about switching to a moderately hypofractionated treatment. The interest in combining stereotactic radiotherapy with systemic treatment, and in particular immunotherapy, is currently being evaluated. Radiological evaluation after stereotactic radiotherapy is quite challenging because of the presence of lesions of radiation pneumonitis which must not be confused with tumour recurrence.
{"title":"Mise au point sur la radiothérapie en conditions stéréotaxiques pour la prise en charge des cancers bronchiques non à petites cellules localisés","authors":"E. Martin , F. Bonnet , M. Rakotosamimanana , C. Chevalier , J. Baude","doi":"10.1016/S1877-1203(25)00065-5","DOIUrl":"10.1016/S1877-1203(25)00065-5","url":null,"abstract":"<div><div>Surgery remains the reference treatment for stage T1-T2 N0 primary non-small cell lung cancer (segmentectomy of lobectomy with lymph nodes dissection). For patients with surgical contraindication or refusing surgery, stereotactic radiotherapy is the standard alternative treatment allowing high local control rate and low toxicity for peripheral lesions. Some complex situations must be identified such as the presence of an interstitial lung fibrosis and the central location with the proximity of hollow organs (bronchi and esophagus), sensitive to high doses per fraction. The ultracentral location is particularly at risk of serious complications and should prompt a discussion about switching to a moderately hypofractionated treatment. The interest in combining stereotactic radiotherapy with systemic treatment, and in particular immunotherapy, is currently being evaluated. Radiological evaluation after stereotactic radiotherapy is quite challenging because of the presence of lesions of radiation pneumonitis which must not be confused with tumour recurrence.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S92-2S97"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236533","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)00069-2
G. Galvaing
The management of locally advanced non-small cell lung cancer (NSCLC), particularly stage III disease, remains a major therapeutic challenge due to its anatomical heterogeneity and the lack of a universal definition for resectability. In recent years, multi-modal strategies—especially neoadjuvant chemoimmunotherapy—have redefined the role of surgery in this complex setting.
Recent data from the CheckMate 816, AEGEAN, and CheckMate 77T trials have shown that adding immunotherapy to neoadjuvant chemotherapy significantly improves pathological complete response rates and event-free survival. These findings support broader surgical indications, even for patients initially deemed unresectable.
Conversion surgery, performed after a favorable response to induction therapy, and salvage surgery, indicated for persistent or recurrent locoregional disease after nonsurgical treatment, both represent curative options in carefully selected patients. These approaches require meticulous evaluation and high-level surgical expertise.
In oligometastatic disease, aggressive local treatment—including resection of the primary tumor and local control of metastases—can lead to significantly improved survival outcomes. Emerging evidence from prospective trials supports the proactive role of surgery in such cases.
{"title":"Place de la chirurgie dans le traitement du CBNPC localement avancé","authors":"G. Galvaing","doi":"10.1016/S1877-1203(25)00069-2","DOIUrl":"10.1016/S1877-1203(25)00069-2","url":null,"abstract":"<div><div>The management of locally advanced non-small cell lung cancer (NSCLC), particularly stage III disease, remains a major therapeutic challenge due to its anatomical heterogeneity and the lack of a universal definition for resectability. In recent years, multi-modal strategies—especially neoadjuvant chemoimmunotherapy—have redefined the role of surgery in this complex setting.</div><div>Recent data from the CheckMate 816, AEGEAN, and CheckMate 77T trials have shown that adding immunotherapy to neoadjuvant chemotherapy significantly improves pathological complete response rates and event-free survival. These findings support broader surgical indications, even for patients initially deemed unresectable.</div><div>Conversion surgery, performed after a favorable response to induction therapy, and salvage surgery, indicated for persistent or recurrent locoregional disease after nonsurgical treatment, both represent curative options in carefully selected patients. These approaches require meticulous evaluation and high-level surgical expertise.</div><div>In oligometastatic disease, aggressive local treatment—including resection of the primary tumor and local control of metastases—can lead to significantly improved survival outcomes. Emerging evidence from prospective trials supports the proactive role of surgery in such cases.</div></div>","PeriodicalId":53645,"journal":{"name":"Revue des Maladies Respiratoires Actualites","volume":"17 2","pages":"Pages 2S121-2S126"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236537","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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