Therapeutic strategies to overcome EGFR mutations as acquired resistance mechanism in ALK-rearranged non-small-cell lung cancer: Case Reports.

Introduction: ALK tyrosine kinase inhibitors (ALK TKIs) have improved prognosis in ALK-rearranged (ALK +) non-small-cell lung cancer (NSCLC). However, drug resistance mechanisms occur inevitably during the course of treatment leading to disease progression. Activation of epidermal growth factor receptor (EGFR) bypass signaling pathway is an uncommon cause of acquired resistance to ALK TKIs. Method: We present two patients with EML4-ALK rearranged NSCLC, developing an acquired EGFR resistance mutation after receiving multiple lines of ALK TKIs. Results: While preclinical models have showed encouraging data, there is a critical need for clinical studies on treatment strategies to overcome this drug resistance. Three real-life therapeutic approaches were used in this report: i) using brigatinib, an inhibitor targeting both ALK and EGFR tyrosine kinases; ii) combining two ALK TKIs together; and iii) delivering doublet platinum chemotherapy. In case 1, time to treatment failure (TTF) was 9.5 months with brigatinib; in case 2, TTF was 10 months with combined TKIs (osimertinib and brigatinib), whereas TTF with chemotherapy was only 2 months. Tolerability profile TKIs combotherapy was acceptable. Conclusion: These case reports underline the therapeutic complexity of EGFR-acquired resistance mutation in ALK+ NSCLC and offers some leads to solve this real-life clinical challenge.

PDL1-status predicts primary resistance of metastatic, EGFR-mutated non small cell lung cancers to EGFR tyrosine-kinase inhibitors.

BACKGROUND: EGFR tyrosine-kinase inhibitors (TKIs) are the reference treatment for metastatic, EGFR-mutated, non-small-cell lung cancers (EGFRm NSCLCs). However, 16-20% of those tumors progress early (3-6 months) and factors predicting that resistance are unknown. This study was undertaken to examine PDL1 status as such a factor. METHODS: This retrospective analysis included metastatic, EGFRm-NSCLC patients who received first-line 1st-, 2nd- or 3rd-generation EGFR TKIs with PDL1 expression determined in pretreatment biopsies. Kaplan-Meier estimations of probabilities of progression-free survival (PFS) and overall survival (OS) were compared with log-rank test, and logistic-regression analyses. RESULTS: PDL1 status of the 145 included patients was ≥1% (47%), 1-49% (33%) or ≥50% (14%). For PDL1-positive vs PDL1-negative patients, respectively, median PFS lasted 8 (95% CI: 6-12) vs 12 (95% CI: 11-17) months (p = 0.008), with 18% vs. 8% (NS) of NSCLCs progressing at 3 months, and 47% vs. 18% (HR 0.25 [95% CI 0.10-0.566], p<0.001) at 6 months. Multivariate analysis retained 1st- or 2nd-generation EGFR TKI, brain metastases and albuminemia <35 g/L at diagnosis as significantly associated with shorter PFS, but not PDL1 status, which was independently associated with progression at 6 months (HR 3.76 [1.23-12.63], p = 0.02). PDL1-negative and PDL1-positive patients' OS lasted 27 (95% CI 24-39) and 22 (95% CI 19-41) months, respectively (NS). Multivariate analysis retained only brain metastases or albuminemia <35 g/L at diagnosis as being independently associated with OS. CONCLUSION: PDL1 expression ≥1% seems to be associated with early progression during the first 6 months of first-line EGFR-TKI treatment of metastatic EGFRm NSCLCs, without impacting OS.

Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti-Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRASG12C-Mutant Lung Cancer.

INTRODUCTION: Sequential anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in NSCLC. KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs. METHODS: This is a multicenter, retrospective study of consecutive advanced KRASG12C-mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (National Cancer Institute Common Classification Criteria for Adverse Events-Version 5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti-PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti-PD-(L)1 as last line of treatment before sotorasib initiation. RESULTS: We identified 102 patients who received sotorasib, including 48 (47%) in the sequence group and 54 (53%) in the control group. Patients in the control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in the sequence group compared with those in the control group (50% versus 13%, p < 0.001). Severe sotorasib-related AEs occurred in 24 patients (24 of 48, 50%) in the sequence group, and among them 16 (67%) experienced a severe sotorasib-related hepatotoxicity. Severe sotorasib-related hepatotoxicity was threefold more frequent in the sequence group compared with that in the control group (33% versus 11%, p = 0.006). No fatal sotorasib-related hepatotoxicity was reported. Non-liver severe sotorasib-related AEs were significantly more frequent in the sequence group (27% versus 4%, p < 0.001). Severe sotorasib-related AEs typically occurred in patients who received last anti-PD-(L)1 infusion within 30 days before sotorasib initiation. CONCLUSIONS: Sequential anti-PD-(L)1 and sotorasib therapy are associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion.

RET-MAP: An International Multicenter Study on Clinicobiologic Features and Treatment Response in Patients With Lung Cancer Harboring a RET Fusion.

INTRODUCTION: Nearly 1% to 2% of NSCLCs harbor RET fusions. Characterization of this rare population is still incomplete. METHODS: This retrospective multicenter study included patients with any-stage RET positive (RET+) NSCLC from 31 cancer centers. Molecular profiling included DNA/RNA sequencing or fluorescence in situ hybridization analyses. Clinicobiological features and treatment outcomes (per investigator) with surgery, chemotherapy (CT), immune checkpoint blockers (ICBs), CT-ICB, multityrosine kinase inhibitors, and RET inhibitors (RETis) were evaluated. RESULTS: For 218 patients included between February 2012 and April 2022, median age was 63 years, 56% were females, 93% had adenocarcinoma, and 41% were smokers. The most frequent fusion partner was KIF5B (72%). Median tumor mutational burden was 2.5 (range: 1-4) mutations per megabase, and median programmed death-ligand 1 expression was 10% (range: 0%-55%). The most common metastatic sites were the lung (50%), bone (43%), and pleura (40%). Central nervous system metastases were found at diagnosis of advanced NSCLC in 21% of the patients and at last follow-up or death in 31%. Overall response rate and median progression-free survival were 55% and 8.7 months with platinum doublet, 26% and 3.6 months with single-agent CT, 46% and 9.6 months with CT-ICB, 23% and 3.1 months with ICB, 37% and 3 months with multityrosine kinase inhibitor, and 76% and 16.2 months with RETi, respectively. Median overall survival was longer in patients treated with RETi versus no RETi (50.6 mo [37.7-72.1] versus 16.3 mo [12.7-28.8], p < 0.0001). CONCLUSIONS: Patients with RET+ NSCLC have mainly thoracic and bone disease and low tumor mutational burden and programmed death-ligand 1 expression. RETi markedly improved survival, whereas ICB may be active in selected patients.

Characterization of lung cancers in patients with BRCA germline variants: A multicenter series.

INTRODUCTION: BRCA1 and BRCA2 (BReast CAncer susceptibility genes) are two tumor-suppressor genes associated with the hereditary breast and ovarian cancer susceptibility syndrome. Recent studies also suggest an increased lung adenocarcinoma risk in carriers. METHODS: We conducted a multi-center retrospective study in 18 different French pulmonology and/or oncology departments on medico-administrative and clinical data prospectively collected in the Clinical Data Warehouse (CDW) of Greater Paris University Hospitals (Assistance Publique-Hôpitaux de Paris, AP-HP). Clinical characteristics and outcomes of patients with LC and a previously known BRCA1/2gl variant were retrospectively evaluated. RESULTS: 17 patients with LC and known BRCA1/2gl variant were included. Patients were most women, former smokers with localized disease and BRCA2 variants. All LC were adenocarcinoma. For patients with medical history of cancer, median time from the first cancer in the BRCA spectrum and the LC occurrence was 20 years. Median disease-free survival (DFS) and overall survival (OS) in localized tumor (Stage I and II) was not reached and 78.6 months, respectively. In advanced cancer (Stade III and IV) median progression free survival was 9.7 months and median OS was 17.8 months. Univariate OS and DFS/PFS analyses by BRCA status did not find significant differences. CONCLUSION: Results seem to show particular LC features in carriers of BRCA2 variants: adenocarcinoma subtype, woman, former or non-smoker.

Histomolecular Resistance Mechanisms to First-Line Osimertinib in EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Multicentric Retrospective French Study.

BACKGROUND: Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used in first line for the treatment of advanced EGFR-mutated non-small cell lung cancer (NSCLC). OBJECTIVE: The identification of related histomolecular resistance mechanisms to first-line osimertinib is a critical step to define the optimal treatment strategy beyond progression. PATIENTS AND METHODS: All consecutive patients treated in the first line with osimertinib for advanced EGFR-mutated NSCLC at 10 hospitals in the Greater Paris area between April 2015 and January 2021 were included. Histomolecular data from plasma and tissue samples taken at progression under osimertinib were collected, and all samples were analyzed using DNA next-generation sequencing. Data on objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to treatment discontinuation (TTD) were also collected. RESULTS: Overall, 104 patients were included. Most patients had adenocarcinoma (n = 102, 98%) with an exon 19 EGFR deletion (n = 54, 52%). Forty-two patients (50%) had central nervous system (CNS) metastasis at the time of osimertinib initiation. ORR was 76%, median PFS and OS were 12.6 months and 52 months, respectively, and TTD was 33 months. At the time of analysis, 44 patients (42%) had tumor progression, and among these patients, 27 (61%) contributive samples were available. The most frequent molecular alterations at progression were mesenchymal epithelial transition factor (MET) amplification (15%; n = 4) and EGFR C797S mutation (11%; n = 3). Histological transformation was found in one patient (4%). RNA next-generation sequencing was performed in eight patients and showed a CCDC6-RET fusion in one patient (12%). CONCLUSIONS: We confirmed the efficacy of osimertinib in patients with advanced EGFR mutation-positive NSCLC. At progression, the most frequent histomolecular alterations were MET amplification and EGFR C797S mutation.

Exposure-Response Analysis of Osimertinib in Patients with Advanced Non-Small-Cell Lung Cancer.

High interindividual variability (IIV) of the clinical response to epidermal growth factor receptor (EGFR) inhibitors such as osimertinib in non-small-cell lung cancer (NSCLC) might be related to the IIV in plasma exposure. The aim of this study was to evaluate the exposure−response relationship for toxicity and efficacy of osimertinib in unselected patients with advanced EGFR-mutant NSCLC. This retrospective analysis included 87 patients treated with osimertinib. Exposure−toxicity analysis was performed in the entire cohort and survival analysis only in second-line patients (n = 45). No significant relationship between occurrence of dose-limiting toxicity and plasma exposure was observed in the entire cohort (p = 0.23, n = 86). The median overall survival (OS) was approximately two-fold shorter in the 4th quartile (Q4) of osimertinib trough plasma concentration (>235 ng/mL) than in the Q1−Q3 group (12.2 months [CI95% = 8.0−not reached (NR)] vs. 22.7 months [CI95% = 17.1−34.1]), but the difference was not statistically significant (p = 0.15). To refine this result, the exposure−survival relationship was explored in a cohort of 41 NSCLC patients treated with erlotinib. The Q4 erlotinib exposure group (>1728 ng/mL) exhibited a six-fold shorter median OS than the Q1−Q3 group (4.8 months [CI95% = 3.3-NR] vs. 22.8 months (CI95% = 10.6−37.4), p = 0.00011). These results suggest that high exposure to EGFR inhibitors might be related to worse survival in NSCLC patients.

Invited editorial: Q and A on hereditary lung cancer.

Advances in the field of genetic susceptibility to respiratory diseases (e.g. pulmonary fibrosis, emphysema, cystic fibrosis, pulmonary hypertension) have led pneumologists to integrate the familial risk dimension and work with genetics clinical teams and laboratories. Paradoxically, while thoracic oncologists look on a daily basis for acquired oncogenic alterations in non small cell lung cancer (NSCLC), they know little about inherited, genetic susceptibility to the disease. As a result, collaboration networks with clinical cancer geneticists are poorly developed in thoracic oncology. Faced with this observation, it seemed important to us to address this issue in a very practical way with this "Q and A on Hereditary Lung Cancer" editorial.

[Central nervous system disorders on lorlatinib: How to detect and manage in practice?] / Troubles du système nerveux central sous lorlatinib : comment les détecter et les gérer en pratique ?

The therapeutic arsenal for advanced ALK positive non-small cell lung cancer has been enriched by specific treatments targeting this molecular abnormality, with five molecules available, including lorlatinib, approved since July 2020. This treatment can have side effects common to other tyrosine kinase inhibitors, as well as other less common disorders affecting the central nervous system such as impaired cognitive function, speech or mood. The prevalence of neuro-psychiatric effects under treatment with lorlatinib reported in studies is nearly 40 % with a mild to moderate intensity in most cases. Given the potential impact on patients' quality of life and even on compliance with treatment, it is essential to include their detection during consultations. The main problem is still to have simple screening tools adapted to clinical practice. A multidisciplinary expert panel (pulmonologist, medical oncologist, psychiatrist, neurologist, pharmacist, nurse) therefore met to propose, based on data from the literature and their clinical experience, elements of management in order to detect these cognitive disorders at an early stage and optimize treatment tolerance. The subjects discussed concern screening and assessment tools, the management of side effects, and their prevention. The use of the practical elements proposed by the group could help optimize the identification and management of central nervous system disorders occurring on lorlatinib.

Anti-programmed death ligand 1 immunotherapies in cancer patients with pre-existing systemic sclerosis: A postmarketed phase IV safety assessment study.

OBJECTIVES: Cancer patients with pre-existing autoimmune disease, such as systemic sclerosis (SSc), are excluded from clinical trials, so the data on tolerability and efficacy of immune checkpoint inhibitors in these patients are limited. This study investigated the tolerability and efficacy of anti-programmed death ligand 1 (PD (L)1) immunotherapies in patients with pre-existing SSc. METHODS: Scleronco-01 was a multicentre, nationwide, open-label, phase IV observational study, from 2019 to 2021. RESULTS: Seventeen SSc patients receiving treatment for lung carcinoma (n = 13, 77%), head and neck cancer (n = 2, 12%), melanoma (n = 1, 6%), and colorectal carcinoma (n = 1, 6%) were included. The median (interquartile range) patient age was 60 (34-82) years. Fifteen (88%) patients received anti-PD1 (nivolumab and pembrolizumab) and two (12%) anti-PD-L1 (durvalumab). The median follow-up duration was 12 (range, 2-38) months. Four patients (24%) experienced flare-up of SSc symptoms. Ten patients (59%) developed an immune-related adverse event (grade I-II in 11 patients [65%], grade III-IV in one [6%]) without grade V. The overall response rate was 41% (7/17 patients). The median overall survival was 15.8 (95% confidence interval: 7.3 to not reached) months. CONCLUSION: Anti-PD1 or PD-L1 immunotherapies are suitable options for cancer patients with pre-existing SSc. Longer follow-up periods are required for long-term safety analyses.

Anti-PD-1 immune-related adverse events are associated with high therapeutic antibody fixation on T cells.

Immune checkpoint inhibitors (ICI) widely improved the treatment of solid and hematologic malignancies. Yet, a remarkable proportion of patients receiving ICI develop immune related adverse events (irAEs) which are difficult to define as treatment-related. This underlines the need to develop a biomarker to guide irAE diagnosis. We developed a novel flow cytometry assay combining measurement of anti-PD-1 (programmed cell death protein-1) occupancy and evaluation of remaining PD-1 receptor availability with anti-IgG4 PE and anti-PD-1 BV421. We prospectively collected blood and biological fluids samples from patients treated by IgG4 anti-PD-1 therapy (nivolumab or pembrolizumab), with (n=18) or without (n=12) current irAE. We analyzed PD-1+ and IgG4+ staining pattern and MFI values of these parameters on CD4 and CD8 T cells, and IgG4+/PD-1+ MFI ratios are calculated. A higher mean fluorescence intensity IgG4+/PD-1+ ratio was measured on peripheral CD4+ T cells of irAE cases, when compared to controls (p=0.003). ICI-related toxicity is therefore associated with increased therapeutic antibody occupancy of PD-1 receptors on CD4+ T cells. Furthermore, in one case of ICI-related pneumonitis, binding of therapeutic antibody was stronger on lung CD4+ T cell than in blood. In another case of ICI-related encephalitis, the PD-1 receptor occupancy was total on CSF CD4 T cells, but only partial on peripherical CD4 T cells. Our results suggest that flow cytometry monitoring of ICI occupancy can be used in patients treated with monoclonal ICI to guide irAE diagnosis.

Lung cancer is also a hereditary disease.

Pathogenic genetic variants (formerly called mutations) present in the germline of some individuals are associated with a clinically relevant increased risk of developing lung cancer. These germline pathogenic variants are hereditary and are transmitted in an autosomal dominant fashion. There are two major lung cancer susceptibility syndromes, and both seem to be specifically associated with the adenocarcinoma subtype. Li-Fraumeni syndrome is caused by variants in the TP53 tumour-suppressor gene. Carriers are mainly at risk of early-onset breast cancer, sarcoma, glioma, leukaemia, adrenal cortical carcinoma and lung cancer. EGFR variants, T790M in particular, cause the EGFR susceptibility syndrome. Risk seems limited to lung cancer. Emerging data suggest that variants in ATM, the breast and pancreatic cancer susceptibility gene, also increase lung adenocarcinoma risk. As for inherited lung disease, cancer risk is increased in SFTPA1 and SFTPA2 variant carriers independently of the underlying fibrosis. In this review, we provide criteria warranting the referral of a lung cancer patient to the cancer genetics clinic. Pathogenic variants are first identified in patients with cancer, and then in a subset of their relatives. Lung cancer screening should be offered to asymptomatic carriers, with thoracic magnetic resonance imaging at its core.

Local ablative therapy in oncogenic-driven oligometastatic non-small cell lung cancer: present and ongoing strategies-a narrative review.

Oligometastatic (OM) disease is defined by a low metastatic tumor spread. OM non-small cell lung cancer (NSCLC) treatment aims to improve the patient's prognosis and quality of life, in an attempt-to-cure objective. Oncogenic-driven metastatic NSCLC accounts for about 20-25% of NSCLCs, with an ever-increasing number of potentially druggable molecular alterations. Due to specific targeted therapy, the care and prognosis of mutated NSCLC is quite different from non-oncogenic-driven NSCLC. However, OM-NSCLC treatment guidelines do not specifically discuss oncogenic-driven OM-NSCLC patients. We conducted a narrative review regarding retrospective and prospective studies published from inception to May 2020 dealing with oncogenic-driven OM-NSCLC in order to: (I) describe the specific patterns of metastatic spread of oncogenic-driven NSCLC (i.e., bone and pleural tropism in EGFR mutated NSCLC and serous and brain metastases in ALK NSCLC); (II) review the low level of current evidence for local ablative therapy (LAT) strategies in patients with oncogenic-driven OM-NSCLC, focusing on the benefit/risk of tyrosine kinase inhibitors (TKI) and LATs combination and (III) present strategies to help to select the best candidate for an attempt-to-cure approach. Finally, the optimal strategy may be to introduce a targeted therapy, then treat all tumor sites with LAT, and finally continue TKI for unknown prolonged duration in an attempt to prolong progression free survival in most patients, improve overall survival for some patients, and potentially lead to a cancer cure for a few patients.

Strong ALK and PD-L1 positive IHC expression related ALK amplification in an advanced lung sarcomatoid carcinoma: A therapeutic trap?

OBJECTIVES: Immunohistochemistry (IHC) is considered as a screening method for ALK rearrangement thanks to its excellent sensitivity. Strong marking on immunohistochemistry give the go-ahead to start ALK tyrosine kinase inhibitors (ALK TKI). Lack of therapeutic response may then lead to the suspicion of molecular alterations other than ALK rearrangements. METHODS: We present a patient with strong ALK and PD-L1 positive IHC expression lung sarcomatoid carcinoma with initial life-threatening disease progression after beginning ALK TKI. We also review the literature to summarize ALK amplification clinical features and therapeutic management in lung cancers. RESULTS: Fluorescence in situ Hybridization (FISH) revealed ALK amplification on the initial anatomopathological samples. Lack of ALK rearrangement and strong PD-L1 positive IHC expression led to the initiation of immune checkpoint inhibitor (ICI) as a second line of treatment, with an excellent response. CONCLUSION: We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.

Circulating tumour cells as a potential biomarker for lung cancer screening: a prospective cohort study.

BACKGROUND: Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Blood signatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classify undetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could be detected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosed radiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening. METHODS: We did a prospective, multicentre, cohort study in 21 French university centres. Participants had to be eligible for lung cancer screening as per National Lung Screening Trial criteria and have chronic obstructive pulmonary disease with a fixed airflow limitation defined as post-bronchodilator FEV1/FVC ratio of less than 0·7. Any cancer, other than basocellular skin carcinomas, detected within the previous 5 years was the main exclusion criterion. Participants had three screening rounds at 1-year intervals (T0 [baseline], T1, and T2), which involved LDCT, clinical examination, and a blood test for CTCs detection. Participants and investigators were masked to the results of CTC detection, and cytopathologists were masked to clinical and radiological findings. Our primary objective was to test the diagnostic performance of CTC detection using the ISET technique in lung cancer screening, compared with cancers diagnosed by final pathology, or follow up if pathology was unavailable as the gold standard. This study is registered with ClinicalTrials.gov identifier, number NCT02500693. FINDINGS: Between Oct 30, 2015, and Feb 2, 2017, we enrolled 614 participants, predominantly men (437 [71%]), aged 65·1 years (SD 6·5), and heavy smokers (52·7 pack-years [SD 21·5]). 81 (13%) participants dropped out between baseline and T1, and 56 (11%) did between T1 and T2. Nodules were detected on 178 (29%) of 614 baseline LDCTs. 19 participants (3%) were diagnosed with a prevalent lung cancer at T0 and 19 were diagnosed with incident lung cancer (15 (3%) of 533 at T1 and four (1%) of 477 at T2). Extrapulmonary cancers were diagnosed in 27 (4%) of participants. Overall 28 (2%) of 1187 blood samples were not analysable. At baseline, the sensitivity of CTC detection for lung cancer detection was 26·3% (95% CI 11·8-48·8). ISET was unable to predict lung cancer or extrapulmonary cancer development. INTERPRETATION: CTC detection using ISET is not suitable for lung cancer screening. FUNDING: French Government, Conseil Départemental 06, Fondation UNICE, Fondation Aveni, Fondation de France, Ligue Contre le Cancer-Comité des Alpes-Maritimes, ARC (Canc'Air Genexposomics), Claire de Divonne-Pollner, Enca Faidhi, Basil Faidhi, Fabienne Mourou, Michel Mourou, Leonid Fridlyand, cogs4cancer, and the Fondation Masikini.

[Risk factors and prevention of lung cancer]. / Facteurs de risque et prévention des cancers du poumon.

Risk factors and prevention of lung cancer. In France, lung cancer is the leading cause of death from cancer with more than 30,000 deaths per year. The vast majority (85%) of lung cancer are due to tobacco and the duration of smoking has a greater impact than the amount smoked. Passive smoking increases the risk of lung cancer and is responsible for around 25% of lung cancers in non-smokers in France. The risk of lung cancer linked to cannabis smoke hasn't been demonstrated, but is suspected. Other carcinogens found in certain workplaces, such as asbestos, or in the environment, such as radon in granite soils and urban air pollution, increase the risk of lung cancer. The maximum benefit on lung cancer mortality reduction should be obtained by combining smoking cessation and lung cancer screening by chest CT. Lung cancer screening has shown its effectiveness, but is currently not recommended in France. Measures to promote smoking cessation are known and include public health measures to de-normalize tobacco (neutral packaging, ban on advertising, significant increase in its price) and treatments that have been shown to be effective in smoking cessation: nicotine replacement therapy, varenicline and cognitive behavioral therapy.

Facteurs de risque et prévention des cancers du poumon. En France, le cancer du poumon est la première cause de mortalité par cancer, avec plus de 30 000 décès par an. La très grande majorité (85 %) des cancers du poumon sont dus au tabac. La durée du tabagisme a un impact plus important que la quantité fumée. Le tabagisme passif augmente aussi le risque de cancer du poumon et serait responsable d'environ 25 % des cancers du non-fumeur en France. Le risque de cancer du poumon lié à la fumée de cannabis n'est à ce jour pas démontré mais est suspecté. D'autres cancérogènes trouvés dans certains lieux de travail, tels que l'amiante, ou dans l'environnement, tel que le radon des sols granitiques, et la pollution de l'air des villes peuvent augmenter le risque de cancer du poumon. Le bénéfice maximal sur la réduction de la mortalité par cancer du poumon pourrait être observé par le sevrage tabagique et le dépistage par scanner thoracique. Le dépistage a montré son efficacité, mais n'est pas à ce jour recommandé en France. Les mesures pour favoriser le sevrage tabagique comportent les mesures de santé publique pour dénormaliser le tabac (paquet neutre, interdiction de la publicité, augmentation importante de son prix) et les traitements qui ont démontré leur efficacité dans le sevrage tabagique : la substitution nicotinique, la varénicline et les thérapies cognitives et comportementales.