[The role of endoscopy in the management of peripheral pulmonary nodules, part 2: Treatment]. / Place de l'endoscopie dans la gestion des nodules pulmonaires périphériques, partie 2 : traitement.

The management of peripheral lung nodules is challenging, requiring specialized skills and sophisticated technologies. The diagnosis now appears accessible to advanced endoscopy (see Part 1), which can also guide treatment of these nodules; this second part provides an overview of endoscopy techniques that can enhance surgical treatment through preoperative marking, and stereotactic radiotherapy treatment through fiduciary marker placement. Finally, we will discuss how, in the near future, these advanced endoscopic techniques will help to implement ablation strategy.

[Severe hemoptysis in the onco-hematology patient]. / Hémoptysies sévères du patient d'onco-hématologie.

In France, even though it occurs only exceptionally in cases of hemopathy, severe hemoptysis in cancer is the leading cause of hemoptysis. Without adequate treatment, in-hospital mortality exceeds 60%, even reaching 100% at 6 months. The management of severe hemoptysis should be discussed with the oncologist. Aside from situations of threatening hemoptysis, in which bronchoscopy should be performed immediately, CT angiography is an essential means of localizing the bleeding and determining the causes and the vascular mechanisms involved. In more than 90% of cases, hemoptysis is linked to systemic bronchial or non-bronchial hypervascularization, whereas in fewer than 5%, it is associated with pulmonary arterial origin or, exceptionally, with damage to the alveolar-capillary barrier. The most severely ill patients must be treated in intensive care in centers equipped with interventional radiology, thoracic surgery and, ideally, with interventional bronchoscopy. Interventional radiology is the first-line symptomatic treatment. In over 80% of cases, bronchial arteriography with embolization allows immediate control. Emergency surgery should be avoided, as it is associated with significant mortality. Appropriate and adequate care reduces hospital mortality to 30%, enabling patients to benefit from the most recent, survival-prolonging treatments.

[Advanced bronchoscopic techniques for the diagnosis of peripheral lung nodule]. / Place de l'endoscopie dans les gestions des nodules périphériques. Partie 1 : diagnostic.

The endoscopic diagnosis of peripheral lung nodules is a challenging aspect of oncological practice. More often than not inaccessible by traditional endoscopy, these nodules necessitate multiple imagery tests, as well as diagnostic surgery for benign lesions. Even though transthoracic ultrasonography has a high diagnostic yield, a sizeable complication rate renders it suboptimal. Over recent years, a number of safe and accurate navigational bronchoscopic procedures have been developed. In this first part, we provide an overview of the bronchoscopic techniques currently applied for the excision and diagnostic analysis of peripheral lung nodules; emphasis is laid on electromagnetic navigation bronchoscopy and the association of virtual bronchoscopy planner with radial endobronchial ultrasound. We conclude by considering recent innovations, notably robotic bronchoscopy.

[Potential therapeutic implication of focal adhesion kinase in small-cell lung cancer]. / Implication thérapeutique potentielle de la kinase de l'adhérence focale dans le cancer pulmonaire à petites cellules.

The molecular steps leading to small cell lung cancer (SCLC) development and progression are still poorly understood, resulting in the absence of targeted therapy and an extremely poor prognosis. Activation of Focal Adhesion Kinase (FAK) plays a key role in the invasive behavior of this cancer in vitro. Our hypothesis is that FAK could be a therapeutic target in SCLC. Our work aims to describe a mouse model to study the role of FAK and the antitumoral potential of its inhibition in SCLC in vivo.

[Sotorasib treatment in KRAS G12C-mutated non-small cell lung cancer: Experience in the Tours university hospital]. / Traitement par sotorasib en autorisation d'accès précoce dans le cancer pulmonaire non à petites cellules mutées KRAS G12C : expérience du centre hospitalier régional universitaire de Tours.

Following the CodeBreak 100 study, since 2021 sotorasib has been available in France, with authorization for early access in treatment of non-small cell lung cancer with a KRAS G12C mutation. Our retrospective observational study was designed to determine the efficacy and safety of sotorasib under real-life conditions in patients treated at the Tours CHRU. Our study of 15 patients showed sotorasib to be effective in 47% of cases, with overall survival of 4 months and median progression-free survival of 5.5 months for responders. Tumor control was achieved in 7/8 (87%) of patients with PS of 0 or 1 and in 1/7 (14%) of patients with a PS of 2 or greater. Grade 3 acute hepatitis occurred in 3/15 patients (20%). While sotorasib is an interesting therapeutic option, with efficacy that seems better in patients in good general condition, it entails a possible risk of drug-induced hepatitis, which remains to be specified in dedicated studies.

[Feasibility study: The medical imaging as a tool for therapeutic education in radiotherapy]. / Étude de faisabilité : l'utilisation de l'imagerie médicale en éducation thérapeutique en radiothérapie.

PURPOSE: Assess the feasibility of a randomized controlled trial (RCT) exploring the use of medical imaging as a therapeutic education (TPE) intervention in external radiation therapy. MATERIALS AND METHODS: Experimental feasibility trial of "RCT" type carried out in a single-center, between November 2019 and March 2020, following adult patients treated by thoracic radiotherapy. In addition to the information usually given, the experimental group benefited from an intervention consisting in the visualization of their own medical images using the open-source software "Stone of Orthanc". RESULTS: Forty-nine patients were recruited with a refusal rate of 8.16% (4/49). 20 patients were withdrawn from the study for health reasons (COVID), 10 for medical reasons. All the remaining 15 participants completed the process. Although not significant, the experimental group showed a median gain in the perception of knowledge compared to the control group (+ 1.9 (1.6 - 2.2)) vs (+ 1.4 (1.4 - 1.8)), as well as a decrease in scores related to anxiety (- 3.0 (-4.5 - (-2.0)) vs - 1.0 (-5.0 - 0.0)) and emotional distress ((- 5.0 (- 7.5 - (- 3.5)) vs (- 2.0 (- 5.0 - (- 1.0)) A significant reduction (p=0.043) is observed for the depression score ((- 2.0 (-3.0 - (-1.5)) vs (0.0 (0.0 - 0.0)). CONCLUSION: This study demonstrates the feasibility of the project, with promising preliminary results. Some adaptations in order to conduct a larger-scale RCT are highlighted.

[Immune-related pneumonitis: A differential diagnosis of SARS-CoV-2 pneumonia]. / Pneumopathie immuno-induite : un diagnostic différentiel de la pneumopathie à SARS-CoV-2.

INTRODUCTION: Immune checkpoint inhibitors have revolutionized the management of many cancers and achieved efficacy and durable response for some patients, including those with advanced cancers. However, immunotherapy is associated with side effects caused by the infiltration of immune cells into normal tissues, which can lead to disproportionate dysimmune reactions. While mostly of moderate intensity, these side effects can affect any organ, including the lung, the site of occasionally life-threatening interstitial lung disease. Their presentation can be similar to that of infectious pneumonia (COVID-19). OBSERVATIONS: We report the cases of 3 patients who presented between March and May 2020 with severe pulmonary toxicities secondary to immunotherapy, which led to with an initial hypothesis of SARS-CoV-2 pneumonia. After extensive investigations, the diagnosis of pulmonary toxicity to immunotherapy was given, and the clinical and radiological course following the initiation of corticosteroid therapy was favorable. CONCLUSION: Pulmonary toxicity secondary to immunotherapy remains a rare but potentially life-threatening side effect. The diagnostic approach requires the elimination of several differential diagnoses (infectious process, tumor progression, other etiologies of interstitial lung disease). This adverse event is reversible and evolution after initiation of corticosteroid therapy is usually favorable.

Unrecognized thoracic radiotherapy toxicity: A review of literature.

Radiotherapy remains an important treatment modality for patients with chest malignancies; this is particularly true in patients with breast cancer and Hodgkin lymphoma as well as lung, esophageal, and other mediastinal tumors. More than half of patients with these conditions receive radiotherapy at some point. With the development of new treatment modalities, we are witnessing an improvement of overall survival requiring carefully watching of acute and chronic toxicity of radiation therapy. The challenge is not to ignore radiotherapy's side effects in order to explore and prevent them in the future. Strategies for optimizing thoracic radiotherapy and the advent of innovative techniques may represent an encouraging way to decrease thoracic toxicities. We reviewed the literature to identify these cases of toxicity, which are sometimes forgotten, and others, which have recently been described but remain poorly known.

[Impact of thoracic irradiation on cardiac structures]. / Impact de la radiothérapie thoracique sur les structures cardiaques.

Thoracic irradiation requires protection of the heart as an organ at risk of complications. The mean heart dose is the most studied dosimetric parameter in the literature. Recent studies question its relevance in view of the multiplicity of cardiac injuries, the heterogeneity of the cardiac dose distribution and the current technical possibilities to refine cardiac dosimetric protection. The objective of this literature review is to analyze the available scientific data on the impact of the dose received by the cardiac substructures. A search of articles using the PubMed search engine was used to select the most relevant studies. A total of 19 articles were selected according to pre-established criteria to answer the issue. Several studies found significant associations between dosimetric parameters of substructures and clinical cardiological impact. Some proposed dose constraints for substructures.

[Survival and epidemiological characteristics of women with lung cancer in Reunion]. / Survie et caractéristiques épidémiologiques des femmes atteintes de cancer pulmonaire à La Réunion.

Lung cancer is a common disease throughout the world, representing the main cause of death from cancer. Its incidence in the female population is increasing. In metropolitan France and Reunion Island, the main risk factor remains tobacco smoking. However, environmental, genetic and hormonal factors appear to play a role in bronchial oncogenesis and the survival of affected women is better than that of men. We studied retrospectively the survival and characteristics of a cohort in Reunion Island, diagnosed with lung cancer between January 2017 and December 2018. In total, 501 patients were included over the period including 166 women. The median overall survival was 23 months in women against 11 months in men (P<0.0005). Male sex has been identified as a poor prognostic factor for overall survival (HR=1.338; 95% CI=1.007-1.778) regardless of disease stage. Women smoked less often than men 85.4% of them had adenocarcinoma, with more EGFR mutations than men, and their environmental exposures were lower. The female population of Reunion Island in our study had better overall survival than the men. Smoking status, environmental exposures, histological and molecular characteristics varied by sex.

Corticotropic insufficiency in a monocentric prospective cohort of patients with lung cancer treated with nivolumab: Prevalence and etiology.

INTRODUCTION: Cancer therapy has greatly progressed in the past few years, due to development of immune checkpoint proteins. These immunotherapies, when applied to eligible patients, have significantly reduced mortality but are prone to induce immune side-effects, including pituitary disorder and low adreno-corticotropic hormone (ACTH) and cortisol levels. We aimed to assess the prevalence and etiology of corticotropic insufficiency through a systematic screening of cortisol and ACTH levels in patients with lung cancer treated with nivolumab perfusion. MATERIAL AND METHODS: All patients from our Center with indications for nivolumab treatment for pulmonary squamous cell carcinoma or adenocarcinoma resistant to chemotherapy were successively included and underwent cortisol and ACTH assay before each nivolumab perfusion. When cortisol was below normal without ACTH elevation, we screened for pituitary metastasis, hypophysitis or corticosteroid treatment that could explain the corticotropic insufficiency. RESULTS: Data from 75 patients (80.0% men, 20.0% women) showed 10.7% asymptomatic corticotropic insufficiency, with a mean cortisol level of 2.76±1.27µg/dl. Diagnosis was made during the first 2 months of nivolumab treatment in 88% of cases. Corticosteroid treatment explained the low cortisol level in 25.0% of cases. No pituitary metastases were found. Hypophysitis was suspected in 75.0% of cases. CONCLUSION: In a 75-patient cohort with non-small cell lung cancer treated with the PD1 antibody nivolumab and systematically screened for cortisol abnormalities, 10.7% of patients showed asymptomatic corticotropic insufficiency. Excluding corticotropic insufficiency secondary to corticosteroid treatment, 8.0% of patients presented cortisol level<5µg/dl attributed to hypophysitis. Cortisol screening enables hydrocortisone replacement treatment to be prescribed if necessary, preventing risk of adrenal crisis.

[Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma]. / Dépistage des expositions professionnelles à l'amiante et à la silice par matrice emplois-expositions auprès de patients atteints de cancer bronchopulmonaire et de mésothéliome.

INTRODUCTION: In the context of underreporting of occupational diseases, the aim was to study the validity of silica and asbestos job-exposure matrices in screening occupational exposure in the field of thoracic oncology. METHODS: Fifty patients hospitalized with primitive lung cancer or mesothelioma in a university hospital center in the Hauts-de-Seine department of France were included between November 2016 and September 2017. For each patient 1/the job history was collected, from which data was entered single-blindly into the job-exposure matrices by a resident in occupational medicine, 2/a questionnaire (Q-SPLF) was completed similarly, and 3/the patients also had a consultation with a chief resident in occupational medicine, considered the gold standard. The main outcome was the diagnostic performance of the matrices. The Q-SPLF diagnostic performance was also studied. RESULTS: The asbestos and silica matrices had sensitivities of 100%, specificities of respectively 76.1% and 87.8%, the positive likelihood ratios were at 4.19 [2.5-6] and 8.17 [3.8-10], and the negative likelihood ratios were at 0. The Q-SPLF diagnostic performance was comparable to that of the matrices. CONCLUSIONS: The matrices and the questionnaire have a great diagnostic performance which seems interesting for a use as a screening tool for occupational exposures. These results have yet to be confirmed by large-scale studies.

[Guidelines for the macroscopic management of surgically resected lung carcinoma]. / Recommandations SFP pour la prise en charge macroscopique des pièces de résections de tumeurs pulmonaires.

Gross examination is an essential step for pathological report of a surgical sample. It includes the description of the surgical specimen and their disease(s), the precise and exhaustive sampling of tumoral and adjacent tumoral tissue areas. This examination requires a good knowledge of the updated pTNM classification. Pathologists from the PATTERN group have collaborated with thoracic surgeons, under the auspices of the Sociéte française de pathologie, to propose guidelines for resected specimen management. This approach fits into the context of the elaboration of structured pathological report proposed by the société française de pathologie, which is necessary for a standardized management of patients.

[Stereotactic pulmonary radiotherapy: Which machine?] / Radiothérapie stéréotaxique pulmonaire : quelle machine ?

Stereotactic radiotherapy represents a fundamental change in the practice of radiotherapy of lung cancers. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Stereotactic radiotherapy can be realized either by a dedicated accelerator (CyberKnife®) or by a conventional accelerator associated with specific systems. The two modalities deliver a very precise irradiation whose very good results published to date are similar. Some technical characteristics specific to each type of linear accelerator could guide the choice according to the target volume treated.

LncRNA SNHG4 promotes the proliferation, migration, invasiveness, and epithelial-mesenchymal transition of lung cancer cells by regulating miR-98-5p.

Long noncoding RNA small nucleolar RNA host gene 4 (SNHG4) is usually up-regulated in cancer and regulates the malignant behavior of cancer cells. However, its role in lung cancer remains elusive. In this study, we silenced the expression of SNHG4 in NCI-H1437 and SK-MES-1, two representative non-small-cell lung cancer cell lines, by transfecting them with siRNA (small interfering RNA) that specifically targets SNHG4. We observed significantly inhibited cell proliferation in vitro and reduced tumor growth in vivo after SNHG4 silencing. SNHG4 knockdown also led to cell cycle arrest at the G1 phase, accompanied with down-regulation of cyclin-dependent kinases CDK4 and CDK6. The migration and invasiveness of these two cell lines were remarkably inhibited after SNHG4 silencing. Moreover, our study revealed that the epithelial-mesenchymal transition (EMT) of lung cancer cells was suppressed by SNHG4 silencing, as evidenced by up-regulated E-cadherin and down-regulated SALL4, Twist, and vimentin. In addition, we found that SNHG4 silencing induced up-regulation of miR-98-5p. MiR-98-5p inhibition abrogated the effect of SNHG4 silencing on proliferation and invasion of lung cancer cells. In conclusion, our findings demonstrate that SNHG4 is required by lung cancer cells to maintain malignant phenotype. SNHG4 probably exerts its pro-survival and pro-metastatic effects by sponging anti-tumor miR-98-5p.

Stereotactic radiotherapy in targeted therapy treated oligo-metastatic oncogene-addicted (non-small-cell) lung cancer.

While the prognosis of metastatic non-small-cell lung cancer has shown significant progress these last years, notably with the discovery of oncogen-driven subtypes and the development of targeted therapies, significant improvements are still needed. More recently, numerous authors studied the oligo-metastasis concept, where the metastasis are limited in number and sites involved, and that could benefit from an aggressive approach of these lesions, for instance with the help of stereotactic radiotherapy. Nevertheless, there is no clear consensus existing for the time being for the treatment of these tumors. Three main clinical situations can be distinguished: oligo-metastasis state de novo at diagnosis (synchronous) or as first metastatic event of an initially locally limited affection (metachronous); oligo-progression during systemic treatment of a pluri-metastatic disease; and finally oligo-persistence of some remaining metastatic lesions at the nadir of the systemic therapy effect. In this review, we will discuss the place of stereotactic radiotherapy in the treatment of non-small-cell oligo-metastatic oncogene-addicted cancers treated with targeted therapies, differentiating these three main clinical situations. In all these indications, this technique could provide a benefit in terms of local control, possibly even in specific survival, when associated with targeted therapy continuation, related to local control of the oligo-metastatic cerebral or extracerebral lesions.

[Lung cancer screening among the smoker population]. / Dépistage du cancer du poumon chez les fumeurs.

CONTEXT: Lung cancer is the most common cancer in men and the leading cause of cancer death worldwide. This cancer, often diagnosed at an advanced stage, mainly affects smokers and survival could increase with early detection. Screening by chest x-ray has not shown its effectiveness, then several randomized trials have been carried out about screening by thoracic low-dose computed tomography in smokers. METHODS: A systematic review of these trials was conducted according to the PRISMA criteria as well as a point of the difficulties of setting up screening following these trials. RESULTS: Among five trials that published mortality results, only the US one, the National Lung Screening Trial (NLST) was showed a 20% decrease in lung cancer mortality in smokers screened by low-dose computed tomography compared to chest x-ray. However, besides the lack of power of the other trials, a great heterogeneity of the methods makes the synthesis of the results difficult. While many expert groups are in favor of testing, only the United States has implemented a screening program, whose adherence remains low. CONCLUSION: Many persistent questions about the eligible population, the organization, the side effects, and finally the cost-benefit, need additional research around these issues.

MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF.

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3'-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3'-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K-AKT and epilthelial-mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K-AKT and EMT signaling pathways in human lung cancers.

Ginsenoside metabolite compound K induces apoptosis and autophagy in non-small cell lung cancer cells via AMPK-mTOR and JNK pathways.

Compound K [C-K; 20-O-(ß-d-glucopyranosyl)-20(S)-protopanaxadiol], as a metabolite of ginsenoside, has been verified to have antitumor effects in various cancers, including non-small cell lung cancer (NSCLC). However, the detailed mechanisms of C-K in NSCLC remain largely unknown. In this study, we aimed to evaluate the effect of C-K on apoptosis and autophagy in NSCLC cells as well as its related mechanisms. According to the results, C-K suppressed the proliferation, and led to G1 phase arrest and apoptosis in A549 and H1975 cells. Subsequently, C-K promoted autophagy, as confirmed by the enhanced rate of cells staining positive with acridine orange, increased levels of LC3II and Beclin-1, and with decreased levels of p62 in A549 and H1975 cells. Moreover, 3-methyladenine (3-MA; an inhibitor of autophagy) effectively suppressed the inhibition of proliferation and apoptosis that was induced with C-K. Finally, C-K treatment promoted the activation of the AMPK-mTOR and c-Jun N-terminal kinase (JNK) signaling pathways. Treatment with compound C (AMPK inhibitor) or SP600125 (JNK inhibitor) significantly restrained the inhibition of proliferation, apoptosis, and autophagy induced with C-K in A549 and H1975 cells. In conclusion, this study demonstrates that C-K promotes autophagy-mediated apoptosis in NSCLC via AMPK-mTOR and JNK signaling pathways.