Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI-ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI-ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively ( p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7-73.8%).ICI-ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.This article has supplementary material available from

Background: BRAF mutations occurring in 1%e5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. Patients and methods: Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after 1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was 30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). Results: Of the 118 patients enrolled, 101 presented with a BRAF V600 mutation and 17 with BRAF nonV600 mutations; the median follow-up was 23.9 months. In the BRAF nonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAF V600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%e54.8%]. The ORR had a 99.9% probability of being 30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8e6.8), and OS was 10 months (95% CI 6.8e15.7). The vemurafenib safety profile was consistent with previous publications. Conclusion:Routine biomarker screening of NSCLC should include BRAF V600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAF V600 -mutated NSCLC but not those with BRAF nonV600 mutations. Trial registration: ClinicalTrials.gov identifier: NCT02304809.

Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible serious adverse events. Although severe immune-related adverse events remain rare, they can lead to discontinued treatment or to death if they are not forecasted and managed properly. Even if lung toxicity is not the most frequent adverse event, it remains critical as it can be life-threatening. Herein, the main aspects of pulmonary toxicity are reviewed and guidelines are also proposed in order to manage the possible side-effects.

Introduction: Given the pathophysiology of coronavirus disease 19 (COVID-19), persistent pulmonary abnormalities are likely. Methods:We conducted a prospective cohort study in severe COVID-19 patients who had oxygen saturation <94% and were primarily admitted to hospital. We aimed to describe persistent gas exchange abnormalities at 4 months, defined as decreased diffusing capacity of the lungs for carbon monoxide (DLco) and/or desaturation on the 6-minute walk test (6MWT), along with associated mechanisms and risk factors Results: Of the 72 patients included, 76.1% required admission to the intensive care unit (ICU), while 68.5% required invasive mechanical ventilation (MV). 39.1% developed venous thromboembolism (VTE). At 4 months, 61.4% were still symptomatic. Functionally, 39.1% had abnormal carbon monoxide test results and/or desaturation on 6MWT; high-flow oxygen, MV, and VTE during the acute phase were significantly associated. Restrictive lung disease was observed in 23.6% of cases, obstructive lung disease in 16.7%, and respiratory muscle dysfunction in 18.1%. A severe initial presentation with admission to ICU (p=.0181), and VTE occurrence during the acute phase (p=.0089) were associated with these abnormalities. 41% had interstitial lung disease in computed tomography (CT) of the chest. Four patients (5.5%) displayed residual defects on lung scintigraphy, only one of whom had developed VTE during the acute phase (5.5%). The main functional respiratory abnormality (31.9%) was reduced capillary volume (Vc<70%). Conclusion: Among patients with severe COVID-19 pneumonia who were admitted to hospital, 61% were still symptomatic, 39% of patients had persistent functional abnormalities and 41% radiological abnormalities after 4 months. Embolic sequelae were rare but the main functional respiratory abnormality was reduced capillary volume. A respiratory check-up after severe COVID-19 pneumonia may be relevant to improve future management of these patients.