INTRODUCTION:Optimal first-line immunotherapy duration in metastatic NSCLC with controlled disease remains unclear. We evaluated 6-month nivolumab-ipilimumab (Nivo-Ipi) in patients with disease control (DC). METHODS:This randomized, open-label, noninferiority trial enrolled treatment-naive patients with metastatic NSCLC (aged 18-75 y, Eastern Cooperative Oncology Group performance status 0-1, no actionable genomic alterations). After 6-month induction treatment with Nivo (3 mg/kg biweekly) plus Ipi (1 mg/kg every 6 wk), patients with DC were randomized to continue treatment or stop and resume at disease progression. The primary outcome was progression-free survival (PFS). RESULTS:Among 265 patients enrolled, 71 were randomized to the continuation control arm (n = 36) or to the experimental arm (n = 35), with trial premature interruption because of the lack of European filing for the immunotherapy combination. Median PFS follow-up was 47.8 months (95% confidence interval [CI]: 43.1-51.0). In the per-protocol population, median PFS was 18.7 months (95% CI: 7.1-37.1) in the continuation arm versus not reached (NR) (95% CI: 16.1-NR) in the experimental arm. Median OS was 55.5 months (95% CI: 32.4-NR) in the continuation arm versus NR in the experimental group. The 18-month OS was 80.6% (95% CI: 63.5-90.2) and 93.8% (95% CI: 77.3-98.4), respectively. Grade 3 to 5 treatment-related adverse event rates were higher in the continuation arm (54.3% versus 23.5%). Median time until definitive quality-of-life deterioration was 15.5 months (95% CI: 10.0-NR) for the continuation arm but NR in the experimental arm (hazard ratio = 0.36, 95% CI: 0.14-0.92, p = 0.03). CONCLUSIONS:Stopping Nivo-Ipi combination at 6 months in DC patients demonstrated no survival harm at 4 years, reduced severe immune-related adverse events, and delayed quality-of-life deterioration.

Objective Anti-Ku antibodies (Abs) are rare and detected in various autoimmune diseases (AIDs), presenting in various phenotypes, potentially affecting different organs including the lungs. This study aimed to describe the characteristics and evolution of interstitial lung disease (ILD) in anti-Ku-positive patients. Methods An observational, multicentre, retrospective study was conducted across 10 French University Hospitals between January 2010 and June 2025, including patients with anti-Ku Abs with ILD. Clinical data and all pulmonary function tests and chest CT scans available were reviewed for this study. ILD progression was defined using criteria inspired by the American Thoracic Society/European Respiratory Society/Japenese Respiratory Society/Asociación Latinoamericana de Tórax Clinical Practice Guidelines, applied across the entire follow-up period rather than within the 12-month timeframe, to capture all clinically meaningful progression events. To account for event timing, time to ILD progression was analysed as a time-to-event outcome using Cox proportional hazards models. Results Among 154 anti-Ku-positive patients (51 with idiopathic inflammatory myopathy, 46 with systemic lupus erythematosus, 30 with Sjögren’s disease, 27 with systemic sclerosis), 60 (39%) had ILD (68% women, median age 56 years). The predominant ILD pattern was fibrotic non-specific interstitial pneumonia (27%, n=16). ILD was already present at AID diagnosis in 48 patients (80%). Forty-five (75%) patients progressed after a median time of 4 (2–11) years. Male sex (adjusted HR (aHR) 2.7; 95% CI 1.4 to 5.2) was associated with ILD progression. When the 12-month cut-off was strictly applied, only six patients fulfilled the progressive fibrosing ILD definition. Baseline pulmonary fibrosis was present in 34 (57%) patients and was associated with a reduced survival when adjusting for age at ILD diagnosis and cardiac involvement (aHR 6.5, 95% CI 1.5 to 28.2). Conclusion ILD occurred in 39% of anti-Ku-positive patients and progressed in 75% of them, underscoring the importance of systematic ILD screening and monitoring in these patients.

INTRODUCTION:Osimertinib is a 3rd generation EGFR tyrosine kinase inhibitor, given in 1st line of treatment in advanced EGFR-mutated non-small cell lung cancer (NSCLC). Platinum-doublet chemotherapy for relapsed patients was recommended in 2nd line treatment, until recently. The aim of this retrospective observational multicentric French study was to describe the efficacy of the 2nd line treatments given after progression on osimertinib, before the implementation of the new standard of care based on the results of the Mariposa 2 trial. METHODS:We included all consecutive patients with advanced EGFR-mutated NSCLC treated with osimertinib in 1st line, between March 2018 and March 2023. Then we described the efficacy of the 2nd line treatments received by patients in whom no targetable mechanism of resistance was identified at progression. Best overall response rate (ORR), real-world progression-free survival (rwPFS) and overall survival (OS) were collected. RESULTS:Seventy-two patients were included. Among them, 38 received chemotherapy (CT) alone, 18, chemotherapy + bevacizumab (CB), 6, chemotherapy + osimertinib (CO), 4, chemotherapy + immunotherapy (CI), 4, chemotherapy + immunotherapy + bevacizumab (CIB) and 2, immunotherapy alone (IT). ORRs were CT=42%, CB=55. Median rwPFS were 5.8 months (95% CI 4.2-7.4) and 6.9 months (95% CI 4.5-9.2) for CT and CB respectively, and median OS 13.6 months (95% CI 11.1 - 16.1) and 15.0months (95% CI 11.1-18.9), for CT and CB respectively. CONCLUSION:2nd line therapies received beyond osimertinib monotherapy in metastatic EGFR-mutated patients were mostly CT and CT + Bevacizumab. Recent studies have evaluated new molecules targeting the EGFR protein, offering new prospects for this group of patients.

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease characterized by upper-lobe predominant pleural and subpleural fibrosis and associated with poor prognosis. No evidence-based medical therapy is currently established, and lung transplantation remains the only potentially curative option for selected patients. Antifibrotic agents such as nintedanib and pirfenidone have demonstrated efficacy in other fibrosing interstitial lung diseases, but their role in PPFE remains uncertain. This study aimed to evaluate the clinical outcomes, including lung function decline, survival, and safety, associated with antifibrotic therapy in patients with PPFE in a multicenter setting. We conducted a retrospective multicenter observational study in five expert centers of the French OrphaLung network. Adult patients with a multidisciplinary diagnosis of definite or consistent PPFE were included. Clinical characteristics, imaging findings, lung function tests, treatments, and outcomes were collected from the Colibri database. Patients were categorized according to exposure to antifibrotic therapy (nintedanib or pirfenidone). The primary endpoint was the annualized change in forced vital capacity (FVC). Secondary endpoints included overall survival and treatment tolerability. Lung function trajectories were analyzed using mixed-effects models, and survival was assessed using Kaplan–Meier analysis and Cox regression. A total of 125 patients were included, of whom 70 (56

Experimental data suggest that COVID-19 vaccination could modulate immune checkpoint inhibitor (ICI) effects, but population evidence is limited. Using the French health data system (Système National des Données de Santé), we identified 95,015 adults initiating ICI therapy between December 2020 and March 2023. We assessed mRNA vaccination within 100 days before ICI initiation using inverse probability of treatment weighting and within 100 days after ICI initiation among previously unvaccinated patients using a cloning-censoring-weighting target-trial emulation. The primary outcome was all-cause mortality; secondary outcomes were cancer-specific and non-COVID-19 mortality. Follow-up extended to 31 December 2024 for all-cause mortality and to 31 December 2023 for cause-specific deaths. Pre-ICI mRNA vaccination was associated with lower early all-cause mortality (hazard ratio (HR) 0.90 (95% confidence interval (CI) 0.87-0.94) at 1-3 months and 0.96 (0.93-1.00) at 6 months) and no significant association after 12 months. Post-ICI mRNA vaccination showed a similar early association (HR 0.84 (95% CI 0.80-0.88) at 3 months and 0.86 (0.79-0.94) at 6 months), also with no significant association after 12 months. Estimates for non-COVID-19 and cancer-specific mortality were similar to those for overall survival. Similar early patterns with non-mRNA COVID-19 and other adult vaccines suggest modest, transient associations or healthy-vaccinee effects, rather than a specific mRNA COVID-19 vaccine effect.

Introduction The development of anaplastic lymphoma kinase (ALK) inhibitors transformed the management of ALK fusion-positive (ALK+) non-small cell lung cancer (NSCLC) from a high-mortality disease to a more manageable chronic condition. Methods This quantitative, nationwide French survey collated information via online questionnaires from patients (n=85), caregivers (n=27) and healthcare professionals (HCPs; n=50) on the impact of ALK+ NSCLC on daily lives and psychosocial issues. Results Overall, 46 patients (54%) had received first-line and 39 patients (46%) second-line or later targeted therapy for a mean of 2.4 years. The most common disease-related challenges reported by patients and HCPs were psychological issues (56.5% and 78.0%, respectively), life planning difficulties (50.6% and 64.0%) and limitations in physical activities of daily life (40.0% and 48.0%), respectively. HCPs consistently underestimated the impact of ALK+ NSCLC on patients’ daily lives, especially regarding psychological difficulties, issues with relationships and intimacy, and financial struggles. ALK+ NSCLC had a major impact regarding caregivers’ psychological problems, difficulties in realising life plans, and professional difficulties. The most important patient-rated support and guidance needs were to establish a separate clinic dedicated to nonmedical problems, improve the systematic provision of wellness activities (e.g. yoga), make it easier to report adverse events to the medical team, provide psychological support, and enable exchanges with other patients (e.g. via discussion groups). Conclusions Our study highlights several measures that can be introduced to reduce disease burden and improve quality of life and, besides routine medical follow-up, markedly improve the overall patient journey through ALK+ NSCLC.

Antibody-drug conjugates (ADCs) are rapidly transforming the treatment landscape of advanced non-small cell lung cancer (NSCLC), yet validated predictive biomarkers to guide their use remain lacking. ICARUS-LUNG01 is a prospective, phase II study designed to integrate clinical outcomes with longitudinal translational analyses. In this multicenter trial, 100 pretreated patients with advanced NSCLC received the TROP2-directed ADC datopotamab deruxtecan (Dato-DXd). The study reported an objective response rate (ORR) of 26.0%, with a median progression-free survival (PFS) of 3.6 months, and a greater benefit observed in non-squamous tumors. Baseline and on-treatment tumor analyses suggested that resistance to Dato-DXd could be associated with a lack of TROP2 cytoplasmic staining and the early activation of DNA repair pathways. Conversely, the activation of immune-related pathways was associated with treatment response. Validation of these findings in phase III studies will be essential to define biomarkers, ultimately enabling more precise identification of patients most likely to benefit from Dato-DXd.

BACKGROUND:Chronic pulmonary aspergillosis (CPA) encompasses a spectrum of progressive lung diseases occurring in patients with prior structural lung damage. Despite prolonged antifungal therapy, CPA carries a 5-year mortality of one-third to one-half. Clinical symptoms are nonspecific, and radiological signs often overlap with those of the underlying disease. Direct microscopy and conventional culture are important but insensitive. Consequently, anti-Aspergillus IgG serology is the cornerstone of CPA diagnosis. OBJECTIVES:To review available anti-Aspergillus antibody assays for CPA diagnosis, the factors affecting their performance and interpretation, and their potential role in patient follow-up. SOURCES:PubMed was searched through July 2026 using combinations of 'Aspergillus', 'IgG', 'antibody', 'serology', and 'chronic pulmonary aspergillosis'. Manufacturer documentation was also reviewed for assay characteristics. CONTENT:Multiple enzyme immunoassay platforms exist, alongside manual methods, such as immunoprecipitation, immunoblot, and immunochromatographic tests. Although anti-Aspergillus IgG is central to CPA diagnosis, assay performance and interchangeability remain incompletely characterized. The lack of standardisation in antigen sources (crude extracts versus recombinant proteins; A. fumigatus versus Aspergillus spp.), reported units (Arbitrary Units/mL, IU/mL, mgA/L, mg/L), and manufacturer cut-offs, together with the absence of an international reference standard, prevents cross-assay comparisons. In addition, interpretation is difficult because airway colonisation, particularly in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, and asthma, may yield positive IgG results outside CPA. Moreover, radiological phenotypes, underlying conditions, notably corticosteroid exposure, and causative Aspergillus species contribute to variable sensitivities. IMPLICATIONS:Further work should prioritize assay standardisation, locally validated cut-offs, and evaluation of serial serology alongside imaging, microbiology, and therapeutic drug monitoring.

Diagnosing pulmonary diseases caused by non-fumigatus Aspergillus species remains challenging. We conducted a single-center, retrospective observational study in a French Respiratory Medicine Department. Patients with at least one respiratory sample positive for a non-fumigatus Aspergillus species, without concurrent A. fumigatus isolation over a 12-month period, were included. The primary objective was to determine the prevalence of pulmonary events (colonization or pulmonary diseases) associated with non-fumigatus Aspergillus species. Secondary objectives included species characterization and assessment of positive results for available diagnostic tests, including direct examination and fungal culture from respiratory samples, galactomannan in bronchoalveolar lavage, and serum A. fumigatus-specific IgG. Between April 2017 and January 2022, 497 patients (39.6%) had cultures positive for non-fumigatus Aspergillus species. Among them, 52 (10.5%) experienced pulmonary events: 36 were colonized, and 16 had a documented pulmonary disease. Aspergillus niger was the most frequently isolated species (41%), followed by Aspergillus flavus (27%) and Aspergillus nidulans (10%). Positive results were observed in 10/437 (2.3%) samples for direct examination, 75/808 (9.3%) for fungal culture, 7/94 (7.4%) for galactomannan in bronchoalveolar lavage, and 12/49 (24.5%) for serum Aspergillus fumigatus-specific IgG. Among patients with non-fumigatus Aspergillus positive respiratory samples, most were colonized, while nearly one-third had clinically significant pulmonary diseases, underscoring the clinical relevance of these species. Low positivity rates across diagnostic tests underscore the need for repeated respiratory sampling and fungal culture and suggest that assays primarily designed for A. fumigatus may under-detect these pulmonary events. IMPORTANCE:Non-fumigatus Aspergillus species are recognized as pulmonary pathogens, but their diagnosis is poorly documented. In this 5-year, single-center study, 497 of 1,256 patients had at least one positive respiratory culture for a non-fumigatus species, with 36 considered colonized and 16 with documented lung disease. A. niger, A. flavus, and A. nidulans accounted for almost four-fifths of the isolates. Routine tests produced poor results, with positivity rates of 2.3% for microscopy, 9.3% for repeat culture, 7.4% for bronchoalveolar galactomannan, and 24.5% for Aspergillus fumigatus serum IgG. Overall, the study shows that non-fumigatus species can cause treatable chronic lung disease, but that current diagnostics miss most cases. Until more sensitive tests are available, clinicians must rely on repeated respiratory sampling and culture to identify these infections.

Chronic pulmonary aspergillosis (CPA) is a progressive and potentially fatal lung disease occurring in patients with underlying structural lung damage. Its diagnosis remains challenging because clinical and radiological features are often nonspecific and overlap with pre-existing respiratory conditions. Detection of anti-Aspergillus IgG antibodies is a cornerstone of diagnosis, as microscopy and culture have limited sensitivity. Several serological assays are available, including enzyme-linked immunosorbent assay (ELISA), which is highly sensitive but may lack specificity, and Western blot (WB), for which diagnostic performance data are limited. This study aimed to optimize the serological strategy for CPA diagnosis. The diagnostic performance of a commercial ELISA assay for Aspergillus-specific IgG (Platelia Aspergillus IgG, Bio-Rad) was optimized using serum samples collected at diagnosis from CPA patients and control subjects. Receiver operating characteristic (ROC) curve analysis was performed to assess alternative cut-off values. In parallel, the performance of a commercial WB assay (LDBio) was retrospectively evaluated using serum samples from five groups: CPA, Aspergillus colonization, airway contamination, negative controls with chronic respiratory disease, and healthy donors. ROC curve analysis showed that increasing the ELISA cut-off from 10 to 25 AU/mL maintained excellent sensitivity while improving specificity from 83.5% to 92.8%. The WB assay demonstrated a sensitivity of 87.0% for CPA diagnosis; however, specificity varied depending on the control group, ranging from 41.4% to 60.7%. Adjusting the ELISA threshold to 25 AU/mL significantly enhances diagnostic specificity without compromising sensitivity, whereas WB provides limited additional diagnostic value due to suboptimal specificity.IMPORTANCEChronic pulmonary aspergillosis (CPA) is a severe and often overlooked fungal lung disease that occurs in patients with underlying structural pulmonary disorders. Diagnosis is challenging because clinical and radiological features are frequently nonspecific and overlap with pre-existing lung conditions. Detection of anti-Aspergillus IgG is central to diagnosis, but the optimal interpretation of available assays remains uncertain. In this study, we assessed the diagnostic performance of serological tests using well-defined patient groups reflecting real-world clinical practice. We show that increasing the cut-off of a widely used ELISA assay significantly improves diagnostic specificity without compromising sensitivity. In contrast, our results suggest that a commercial Western blot test provides only limited diagnostic value due to suboptimal specificity, clearly demonstrated using the different patient groups studied. These results help refine the serological strategy for CPA diagnosis and improve its clinical interpretation.

Small-molecule oral Janus kinase (JAK) inhibitors are increasingly used for treatment of digestive and rheumatic inflammatory diseases or haematological disorders. Based on limited data, the risk of tuberculosis (TB) has been reported but considered lower compared with that observed with TNF-α inhibitors a finding we propose to clarify using the WHO VigiBase pharmacovigilance database.We performed a disproportionality analysis of drug-related TB infection using VigiBase. An information component 0.25 (IC0.25) >0 was considered statistically significant. Data were extracted on 09/12/2024. Main characteristics of patients with respiratory infection under JAK and TNF-α inhibitors were analysed.Globally, the mean IC0.25 for TB was 2.0 and 3.2 for JAK and TNFα inhibitors, respectively. Among JAK inhibitors, the risk of TB varied and appeared significant for ruxolitinib, baricitinib, tofacitinib and upadacitinib. A total of 695 patients with TB occurring during JAK inhibitor therapy were included. We observed a higher proportion of reported cases among women (54.7%), aged from 45 to 64 years (35.7%). Extra-thoracic TB involvements were reported in 133 cases (66%). TB cases were most frequently reported among patients receiving tofacitinib (n=330, 47.5%), ruxolitinib (n=217, 31.1%) and upadacitinib (n=102, 14.6%). Overall, 42 patients (5.9%) died with active TB.JAK inhibitors are associated with an increased risk of TB. These results argue to recommend latent TB infection screening and systematic anti-TB preventive therapy even in low endemic countries, before initiating JAK inhibitor therapy.

The c-Met receptor is a key therapeutic target in non-small cell lung cancer (NSCLC). Current methods for assessing c-Met level, are limited by biopsy sampling, which fails to account for spatio-temporal and intra-tumour heterogeneity. This study aims to evaluate the use of PET/CT imaging for non-invasive, full-body quantification of c-Met expression in different subtypes of NSCLC, encompassing both ADC and squamous cell carcinoma and compare it to MET gene alterations and IHC c-Met scoring. [68Ga]Ga-EMP-100, a PET radiotracer targeting c-Met, was radiolabelled and characterized. Cell-Derived Xenograft (CDX) models of NSCLC with different characteristics were developed and validated for PET/CT imaging using [68Ga]Ga-EMP-100. Tumour uptake and heterogeneity were quantified and compared to c-Met expression determined by IHC (H-score using SP44 and EP1454Y antibodies) and MET gene amplification detected by FISH and NGS. Automated radiolabelling of [68Ga]Ga-EMP-100 demonstrated a high radiochemical yield (RCY) and purity (RP). Pharmacokinetics studies revealed rapid excretion predominantly by the renal pathway. PET/CT imaging resulted in high contrast and enabled non-invasive classification of CDX models regarding c-Met receptor levels. The highest tumour uptake was observed in H1648 and EBC-1 models. Although MET gene alterations were not correlated with c-Met protein expression at the cell surface, a good correlation was found between SUVmax and c-Met expression, when using the EP1454Y antibody. PET/CT imaging using [68Ga]Ga-EMP-100 successfully quantified c-Met expression in vivo, clearly adding up to conventional IHC and genetic methods. Our study adds novel comparative evidence across tumour histotypes, providing new insight into how tumour phenotype affects c-Met–targeted imaging. This radiotracer holds potential as a non-invasive tool for selecting patients for c-Met-targeted therapies and monitoring therapeutic response in NSCLC. Further clinical studies are warranted.

Background:Pleuroparenchymal fibroelastosis (PPFE) is a recently described interstitial lung disease associated with multiple diseases. Japanese studies found an association between PPFE and non-tuberculous mycobacterial pulmonary disease (NTM-PD), but no study has been conducted in Europe. We aimed to assess in France the prevalence of PPFE among patients with NTM-PD, and to look for risk factors of PPFE and mortality. Method:We conducted a retrospective cohort study in two French hospitals from January 1, 2020 to March 31, 2022. NTM-PD patients were included if they had at least one chest high-resolution computed tomography (HRCT) scan available, to identify the presence or the occurrence of radiological patterns of PPFE based on established criteria. Risk factors for PPFE and five-year mortality were assessed using univariate and multivariate analyses. Results:A total of 101 patients were included, PPFE was identified in 14 patients (13.9%) and was associated with a lower body mass index (BMI) at diagnosis [odds ratio (OR) 21.4, 95% confidence interval (CI): 3.5-415.3 for BMI <18 kg/m² with PPFE, P<0.001] in multivariate exploratory analysis. Seventy patients had a minimum of two chest HRCT scans spaced by at least 3 years. Among them, 10 had PPFE: 8 at NTM-PD diagnosis, and 1 PPFE developing from pleural caps 9 years later. Five-year mortality could be studied for 71 patients. PPFE was associated with 5-year mortality (OR 6.3, 95% CI: 1.3-29.9, P=0.02) in multivariate exploratory analysis. Conclusions:PPFE is frequently observed among patients with NTM-PD, and seems to be associated with a lower BMI and the 5-year mortality, supporting its systematic screening in this population.

PURPOSE:Radiation-induced lung injury is relatively uncommon but disabling, and a dose-limiting factor in thoracic radiotherapy. This complication is mainly encountered following radiotherapy for lung cancers. We provide recommendations for good clinical practice, defining the prevention and management of radiation-induced lung injury. METHODS:Members of the Association francophone pour les soins oncologiques de support (Afsos; French-speaking association for oncology care and support) and the Société française de radiothérapie oncologique (SFRO, French society for radiation oncology) set up a multidisciplinary working and review group to draft these recommendations for 2023 to 2024, based on a systematic review of the literature. RESULTS:Radiation-induced lung injury comprises several forms, mainly resulting from acute toxicity (radiation pneumonitis) and chronic toxicity (radiation fibrosis). Specific forms can be identified, such as organising pneumonia (formerly bronchiolitis obliterans organizing pneumonia) and radiation recall pneumonia. The risk factors are numerous and include dosimetric risk factors, patient-related factors and tumour-related factors. New challenges include the specific complications of stereotactic radiotherapy, the combination of recent specific oncological treatments including tyrosine kinase inhibitors and immunotherapy, and the association with certain pathologies such as interstitial lung disease. CONCLUSION:The profile of radiation-induced lung injury is evolving with new radiotherapy techniques and innovative systemic oncology treatments. Rapid detection and management of these side-effects are essential for good patient care.