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Cancer immunotherapy combinations have recently been shown to improve the overall survival of advanced mesotheliomas, especially for patients responding to those treatments. We aimed to characterize the biological correlates of malignant pleural mesotheliomas’ primary resistance to immunotherapy and antiangiogenics by testing the combination of pembrolizumab, an anti–PD-1 antibody, and nintedanib, a pan-antiangiogenic tyrosine kinase inhibitor, in the multicenter PEMBIB trial (NCT02856425). Thirty patients with advanced malignant pleural mesothelioma were treated and explored. Unexpectedly, we found that refractory patients were actively recruiting CD3+CD8+ cytotoxic T cells in their tumors through CXCL9 tumor release upon treatment. However, these patients displayed high levels of somatic copy-number alterations in their tumors that correlated with high blood and tumor levels of IL6 and CXCL8. Those proinflammatory cytokines resulted in higher tumor secretion of VEGF and tumor enrichment in regulatory T cells. Advanced mesothelioma should further benefit from stratified combination therapies adapted to their tumor biology. Significance: Sequential explorations of fresh tumor biopsies demonstrated that mesothelioma resistance to anti–PD-1 + antiangiogenics is not due to a lack of tumor T-cell infiltration but rather due to adaptive immunosuppressive pathways by tumors, involving molecules (e.g., IL6, CXCL8, VEGF, and CTLA4) that are amenable to targeted therapies. This article is highlighted in the In This Issue feature, p. 799

Immuno-Histo-Chemistry scoring of baseline tumor biopsies according to their DCB status.

Cytotoxic response in tumor biopsies of patients with No DCB upon combination treatment.

Cancer immunotherapy combinations have recently been shown to improve the overall survival of advanced mesotheliomas, especially for patients responding to those treatments. We aimed to characterize the biological correlates of malignant pleural mesotheliomas’ primary resistance to immunotherapy and antiangiogenics by testing the combination of pembrolizumab, an anti–PD-1 antibody, and nintedanib, a pan-antiangiogenic tyrosine kinase inhibitor, in the multicenter PEMBIB trial (NCT02856425). Thirty patients with advanced malignant pleural mesothelioma were treated and explored. Unexpectedly, we found that refractory patients were actively recruiting CD3+CD8+ cytotoxic T cells in their tumors through CXCL9 tumor release upon treatment. However, these patients displayed high levels of somatic copy-number alterations in their tumors that correlated with high blood and tumor levels of IL6 and CXCL8. Those proinflammatory cytokines resulted in higher tumor secretion of VEGF and tumor enrichment in regulatory T cells. Advanced mesothelioma should further benefit from stratified combination therapies adapted to their tumor biology.Significance:Sequential explorations of fresh tumor biopsies demonstrated that mesothelioma resistance to anti–PD-1 + antiangiogenics is not due to a lack of tumor T-cell infiltration but rather due to adaptive immunosuppressive pathways by tumors, involving molecules (e.g., IL6, CXCL8, VEGF, and CTLA4) that are amenable to targeted therapies.This article is highlighted in the In This Issue feature, p. 799

Background Child exposure to cigarette smoke is harmful. It should be reduced through parental smoking cessation interventions. The aim of our study was to determine the impact of simple advice provided by the pediatrician on the smoking habits of parents of children with cystic fibrosis (CF), diabetes mellitus (DM) and infants hospitalized for bronchiolitis. Methods Parents were interviewed on their smoking habits. Smoking cessation advice was provided by the pediatrician. A new smoking habits assessment was done at three months by phone interviews. Results Two hundred and sixty parents were interviewed (91 in the CF group, 136 in the DM group and 33 in the bronchiolitis group). Seventy parents were active smokers: 33% of parents of children with CF, 23.5% of parents of children with DM and 24.2 % for those with infants hospitalized for bronchiolitis (p = 0.42). In the CF group, smoking cessation had been significantly more frequently discussed with the medical team previously. Sixty-seven smoking parents (95.7%) answered the 3-month assessment: 29.8% reported having started a smoking cessation process; 10.4% had quit smoking. The quitting rate was significantly higher in the groups of patients followed for a respiratory disorder (37.5% for bronchiolitis, 15% for CF versus 0% for DM, p= 0.005). Conclusion This study shows the important role that information and simple advice from pediatricians can have in initiating smoking cessation in parents of patients followed in specialized clinics or who are hospitalized, with a greater efficiency in parents of patients suffering from lung disorders. This article is protected by copyright. All rights reserved.

Introduction: Although frequent in NSCLC, patients with brain metastases (BMs) are often excluded from immune checkpoint inhibitor (ICI) trials. We evaluated BM outcome in a less-selected NSCLC cohort.Methods: Data from consecutive patients with advanced ICI-treated NSCLC were collected. Active BMs were defined as new and/or growing lesions without any subsequent local treatment before the start of ICI treatment. Objective response rate (ORR), progression-free survival, and overall survival (OS) were evaluated. Multivariate analyses were performed by using a Cox proportional hazards model and logistic regression.Results: A total of 1025 patients were included; the median follow-up time from start of ICI treatment was 15.8 months. Of these patients, 255 (24.9%) had BMs (39.2% active, 14.3% symptomatic, and 27.4% being treated with steroids). Disease-specific Graded Prognostic Assessment (ds-GPA) score was known for 94.5% of patients (35.7% with a score of 0-1, 58.5% with a score of 1.5-2.5, and 5.8% with a score of 3). The ORRs with BM versus without BM were similar: 20.6% (with BM) versus 22.7% (without BM) (p = 0.484). The intracranial ORR (active BM with follow-up brain imaging [n = 73]) was 27.3%. The median progression-free survival times were 1.7 (95% confidence interval [CI]: 1.5-2.1) and 2.1 (95% CI: 1.9-2.5) months, respectively (p = 0.009). Of the patients with BMs, 12.7% had a dissociated cranial-extracranial response and two (0.8%) had brain pseudoprogression. Brain progression occurred more in active BM than in stable BM (54.2% versus 30% [p Conclusion: In multivariate analysis BMs are not associated with a poorer survival in patients with ICI-treated NSCLC. Stable patients with BM without baseline corticosteroids and a good ds-GPA classification have the best prognosis. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Introduction This randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD-L1) antibody atezolizumab in SCLC progressing after first-line platinum–etoposide chemotherapy. Methods Patients were randomized 2:1 to atezolizumab (1200 mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to 6 cycles of topotecan or re-induction of initial chemotherapy). Patients were not selected based on PD-L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two-stage design with 2:1 randomization and O'Brien-Fleming stopping rules was used. The null hypothesis was rejected if more than 12 of 45 patients were responders. Results Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% confidence interval [CI]: 0.0–6.8), whereas 8 others had stable disease (20.9% disease control rate; 95% CI: 8.8–33.1). Among eligible chemotherapy patients (n = 20), 10% achieved an objective response (65% disease control rate). Median progression-free survival was 1.4 months (95% CI: 1.2–1.5) with atezolizumab and 4.3 months (95% CI: 1.5–5.9) with chemotherapy. Overall survival did not significantly differ between groups. Median overall survival was 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively (adjusted hazard ratioatezolizumab : 0.84, 95% CI: 0.45–1.58; p = 0.60). Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD-L1 staining (SP142 clone). Conclusions Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed.

Resume Introduction Les inhibiteurs de point de controle immunitaire sont de plus en plus largement utilises dans la therapeutique anticancereuse avec une extension des indications. Leur toxicite est polymorphe, comprenant des atteintes dysimmunitaires specifiques d’organe et le developpement plus rare d’atteintes systemiques. Observations Nous rapportons 3 cas de granulomatose sarcoidosique developpee durant un traitement par inhibiteurs de point de controle immunitaire (dans des tumeurs primitives differentes : adenocarcinome bronchique, cancer bronchique a petites cellules et melanome). La presentation radioclinique et la gravite de l’atteinte etaient variables. Le diagnostic reposait sur l’examen anatomo-pathologique et l’elimination des diagnostics differentiels, notamment infectieux. Dans ce cas, l’immunotherapie doit etre stoppee et sa re-administration ulterieure reste a determiner. Une corticotherapie systemique est discutee selon l’intensite des symptomes. Conclusions La connaissance de cette toxicite est primordiale car les signes clinico-radiologiques peuvent faire evoquer une progression tumorale.

EVIDENS is an ongoing, prospective, non-interventional study evaluating the effectiveness and safety of nivolumab in lung cancer patients in France (ClinicalTrials.gov NCT03382496). Adults with a pathologically confirmed diagnosis of lung cancer and initiating treatment with nivolumab were recruited from 146 sites in France. This analysis included only patients with non-small cell lung cancer (NSCLC) who received ≥1 nivolumab infusion, and evaluated patient characteristics at the time of nivolumab initiation and its effectiveness and safety after a median follow-up of 18 months. A total of 1,420 patients with NSCLC were included, most of whom had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1 (82.9%), non-squamous histology (69.2%) and stage IV disease (91.4%). Brain metastases were present in 19.9% of patients. Nivolumab was a second-line or ≥third-line regimen in 73.6% and 26.1% of patients, respectively. Almost all patients had prior chemotherapy (99.7%). Median overall survival was 11.2 months (95% confidence interval [CI]: 10.0–12.4). ECOG PS, smoking status, corticosteroids at baseline, epidermal growth factor receptor mutation status, presence of symptomatic brain metastases and treatment-related adverse events (TRAEs) were independent predictors of survival. Grade 3 and 4 TRAEs were reported in 105 (7.4%) and 12 (0.8%) patients, respectively; no treatment-related deaths were reported. Preliminary results of the EVIDENS study confirm the effectiveness and safety of nivolumab, mostly in pre-treated advanced NSCLC patients, with similar benefits to those observed in the phase III randomized clinical trials, despite a broader study population.

Background: The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab. Methods: 68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the TP53, RB1, NOTCH1, NOTCH2, and NOTCH3 genes. ctDNA was detectable when at least one somatic mutation was identified, and its relative abundance was quantified by the variant allele fraction (VAF) of the most represented mutation. Results: We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49, 65.3%) and RB1 (25/49, 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm. Conclusion: ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.

In oncology clinical research, the analysis and reporting of adverse events is of major interest. A consistent depiction of the safety profile of a new treatment is as crucial in establishing how to use it as its antitumor activity. The advent of new therapeutics has led to major changes in the management of patients and targeted therapies or immune checkpoint inhibitors are administered continuously for months or even years. However, the classical methods of adverse events analysis are no longer adequate to properly assess their safety profile. Indeed, the worst grade method and time-to-event analysis cannot capture the duration or the evolution of adverse events induced by extended treatment durations. Many authors have highlighted this issue and argue that the analysis of safety data from clinical trials should be modernized by considering the dimension of time and the recurrent nature of adverse events. This paper aims to illustrate the limitations of current methods and discusses the value of alternative approaches such as the prevalence function, Q-TWiST, the ToxT and the recurrent event approaches. The rationale and design of the MOTIVATE trial, which aims to model the evolution of toxicities over time using the prevalence function in patients treated by immunotherapy, is also presented ( ClinicalTrials.gov Identifier: NCT03447483; Date of registration: 27 February 2018).

We report the case of a 28-year-old woman admitted with acute respiratory failure. The patient had no personal or familial medical history involving respiratory disease as asthma, thrombotic events or bleeding. She was a heavy smoker (15 cigarettes per day for the past five years) and “vaped” electronic-cigarettes (e-cigarettes) one month prior to the incident. She consumed 10 mL of e-liquid bottle with nicotine salt (12 mg·mL−1) in two days. No cannabidiol (CBD) or tetrahydrocannabinol (THC) was detected. No other home-made components were added. The patient did not take any regular medicines or contraceptives. No consumption of cannabis, cocaine or any other drugs was reported (confirmed with negative urinary drug test). Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Villeneuve has nothing to disclose. Conflict of interest: Dr. Le Borgne has nothing to disclose. Conflict of interest: Dr. Colombat has nothing to disclose. Conflict of interest: Dr. Collot has nothing to disclose. Conflict of interest: Dr. Ruiz has nothing to disclose. Conflict of interest: Dr. Lanot has nothing to disclose. Conflict of interest: Dr. Brouchet has nothing to disclose. Conflict of interest: Dr. Rabeau has nothing to disclose. Conflict of interest: Dr. Noel-Savina has nothing to disclose. Conflict of interest: Dr. Didier reports personal fees from Astra Zeneca, personal fees from GSK, personal fees from ALK, personal fees from Novartis, personal fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr. Prevot has nothing to disclose.

BackgroundWe report the results from the advanced malignant mesothelioma (aMM) expansion cohort of the PEMBIB Phase Ib trial (NCT02856425) evaluating the safety, efficacy & biomarkers of an antiangiogenic tyrosine kinase inhibitor (nintedanib) with an anti-PD1 immunotherapy (pembrolizumab).MethodsPatients with aMM relapsing after at least one line of platinum doublet chemotherapy and not previously pre-exposed to IO were treated with a combination of oral nintedanib (150mg BID) & IV pembrolizumab (200mg Q3W) with a 7 days nintedanib lead-in preceding pembrolizumab initiation. Baseline and on-treatment (cycle D2, day 1 [C2D1]) fresh tumor & blood samples were prospectively phenotyped by flow cytometry (FC). RNAseq was run on tumor samples. Immune factors were titrated on tumor secretome and plasma.Results30 aMM patients were treated and 29 evaluable for response. Median age was 68 years old (38–85) and 86% of aMM were epithelioid. The most frequent adverse events (AE) (grades 1–3) related to the combination were liver enzymes increase, fatigue, nausea, and diarrhea. 4 (13.3%) patients developed grade 3–5 immune- related AE. Patients died of cancer progression (n=14, 46.7%), myocarditis with thrombo-embolic event (n=1, 3.3%) and COVID-19 (n=1, 3.3%). Median follow-up was 14.8 months (95%CI [9.70–18.2]). Best Overall Response Rates (BORR) per RECISTv1.1 were Partial Response (PR, n=7/29; 24.1%), Stable Disease (SD, n=17/29; 58.6%) and Progressive Disease (n=5/29; 17.2%). Disease Control Rate (DCR) (defined as PR + SD) was 46.6% at 6 months. Patients with DCR at 6 months had significantly higher percentage of PDL1 expression on tumor cells (by Immuno-Histo-Chemistry, antibody clone SP263) and higher CD8+ T cells infiltrate in tumor biopsies (by FC) at screening. Upon treatment, soluble plasma rate of CXCL9 and CXCL13 increased in all patients, as well as tumor immune infiltrates estimated by deconvolution of tumor biopsies RNA-seq. But deconvoluted estimates of NK cells, T cells and myeloid dendritic cells infiltrates on baseline tumors and C2D1 biopsies were higher in patients with DCR at 6 months. Pre & on-treatment IL6 and IL8 rates in tumor secretome & plasma were higher in patients without DCR. Gene Set Enrichment Analyses on RNA-seq from screening biopsies highlighted an enrichment in E2F, MYC and KRAS gene pathways and lower expression of type 1 interferon signature in patients without DCR than those with DCR at 6 months.ConclusionsWith a BORR of 24% and a DCR of 47% at 6 months, pembrolizumab and nintedanib combination provided valuable therapeutic benefits for patients with aMM.Trial RegistrationClinicalTrialsgov, NCT02856425. Registered August 4, 2016 — Prospectively registered,https://clinicaltrials.gov/ct2/show/NCT02856425?term=PEMBIB&draw=2&rank=1.Ethics ApprovalThe protocol was first approved by the Agence Nationale de Sécurité du Médicament (ANSM) on June 24th 2016 (Ref #160371A-12). The protocol was also approved by the Ethical Committee (Comité de Protection des Personnes Ile de France 1) on Jul 12th 2016 (Ref #2016-mai-14236ND).

Background: We report the results from the advanced malignant mesothelioma (aMM) expansion cohort of the PEMBIB phase Ib trial (NCT02856425) evaluating the safety, efficacy & biomarkers of an antiangiogenic TKI (nintedanib = [N]) with an anti-PD1 immunotherapy (pembrolizumab = [P]). Methods: Patients (Pts) with aMM that relapsed after at least one line of platinum-based combination were treated with a combination of oral [N] (150mg BID) & IV [P] (200mg Q3W) with 7 days [N] lead-in preceded [P] initiation. Baseline and on-treatment fresh tumor & blood samples were prospectively phenotyped immune cells by flow cytometry (FC). RNAseq was run on tumor samples. Immune factors were titrated by multiplex ELISA on tumor secretome and plasma. Results: 30 aMM Pts were treated and 29 evaluable for response. Median age was 68 years old (38-85) and 86% of aMM were epithelioid. The most frequent adverse events (AE) (grades 1-3) related to the combination were liver enzymes increase, fatigue, nausea and diarrhea. 4 (13.3%) Pts developed grade 3-5 immune- related AE. Patients died of cancer progression (n=14), myocarditis with thrombo-embolic event (n=1) and COVID-19 (n=1). Median follow-up was 14.8 months (95%CI [9.70-18.2]). Best Overall Response Rates (BORR) were Partial Response (PR;n=7), Stable Disease (SD;n=17) and Progressive Disease (PD;n=5). Disease Control Rate (DCR) (defined as PR + SD) was 68.4% and 46.6% at 3 and 6 months, respectively. Analyses on fresh tumor biopsies showed that all patients increased their CD3+ T-cells and circulating levels of soluble PD1 and CXCL9 under treatment. Pts developing PR had significantly higher CD45+ and CD3+ tumor infiltrative cells at baseline compared to Pts with SD & PD as BORR. Pts with DCR at 6 months had significantly higher expression of integrins on circulating effector memory CD4+ & CD8+ T cells by FC, and higher NK, T, and myeloid dendritic cells infiltrates on baseline tumor RNAseq. Pre & on-treatment IL6 and IL8 levels in tumor secretome & plasma were higher among Pts with PD. Conclusions: With a BORR of 23% and a DCR of 47% at 6 months, [P]+[N] combination provided valuable therapeutic benefits for Pts with aMM. Flow cytometry and secretome on fresh baseline tumor biopsies are simple techniques which could be used to predict treatment efficacy in aMM Pts. Clinical trial identification: NCT02856425. Legal entity responsible for the study: Gustave Roussy. Funding: Funding: Boehringer Ingelheim;Drug supply: Boehringer Ingelheim & MSD;Sponsor: Gustave Roussy. Disclosure: C. Baldini: Financial Interests, Personal, Invited Speaker: Sanofi;Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Research Grant: Seattle Genetics;Financial Interests, Institutional, Research Grant: Iteos;Financial Interests, Institutional, Invited Speaker: Tahio;Financial Interests, Institutional, Research Grant: BMS. N. Chaput: Financial Interests, Institutional, Research Grant: AstraZeneca;Financial Interests, Institutional, Research Grant: BMS;Financial Interests, Institutional, Research Grant: GSK;Financial Interests, Institutional, Research Grant: Roche;Financial Interests, Institutional, Research Grant: Sanofi;Financial Interests, Institutional, Research Grant: Cytune Pharma. G. Zalcman: Financial Interests, Personal, Invited Speaker, outside the submitted work: BMS;Financial Interests, Personal, Invited Speaker, outside the submitted work: MSD;Financial Interests, Personal, Invited Speaker, outside the submitted work: AstraZeneca;Financial Interests, Personal, Invited Speaker, outside the submitted work: Boehringer Ingelheim;Non-Financial Interests, Personal, Advisory Board, outside the submitted work: Roche;Non-Financial Interests, Personal, Advisory Board, outside the submitted work: Takeda;Non-Financial Interests, Personal, Advisory Board, outside the submitted work: AstraZeneca;Non-Financial Interests, Personal, Advisory Board, outside the submitted work: AbbVie. C. Massard: Non-Financial Interests, Personal, Advisory Role: Amgen;Non-Financial Interests, Personal, Advisory Role: Astellas Pharma;Non-Financial Interests, Personal, Advisory Role: AstraZeneca;Non-Financial Interests, Personal, Advisory Role: Bayer;Non-Financial Interests, Personal, Advisory Role: BeiGene;Non-Financial Interests, Personal, Advisory Role: BMS;Non-Financial Interests, Personal, Advisory Role: Celgene;Non-Financial Interests, Personal, Advisory Role: Debiopharm Group;Non-Financial Interests, Personal, Advisory Role: Genentech/Roche;Non-Financial Interests, Personal, Advisory Role: Ipsen;Non-Financial Interests, Personal, Advisory Role: Janssen;Non-Financial Interests, Personal, Advisory Role: Lilly;Non-Financial Interests, Personal, Advisory Role: MSD;Non-Financial Interests, Personal, Advisory Role: Novartis;Non-Financial Interests, Personal, Advisory Role: Pfizer;Non-Financial Interests, Personal, Advisory Role: Sanofi;Non-Financial Interests, Personal, Advisory Role: Orion;Non-Financial Interests, Personal, Advisory Role: Taiho Pharmaceuticals;Non-Financial Interests, Personal, Advisory Role: Blueprint Medicinces;Non-Financial Interests, Personal, Advisory Role: Innate Pharma;Non-Financial Interests, Personal, Advisory Role: PharmaMar;Non-Financial Interests, Personal, Advisory Role: Faron Pharmaceuticals. J-C. Soria: Financial Interests, Personal, Stocks/Shares: AstraZeneca;Financial Interests, Personal, Stocks/Shares: Gritstone Oncology;Financial Interests, Personal, Stocks/Shares: Relay Therapeutics;Financial Interests, Personal, Member of the Board of Directors: Hookipa Pharmaceuticals;Financial Interests, Personal, Full or part-time Employment, sept 2017 to dec 2019: AstraZeneca. A. Marabelle: Financial Interests, Personal, Invited Speaker: Roche/Genentech;Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: Merck Serono;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Amgen;Financial Interests, Personal, Invited Speaker: Sanofi;Financial Interests, Personal, Invited Speaker: Servier;Non-Financial Interests, Personal, Principal Investigator: Roche/Genentech;Non-Financial Interests, Personal, Principal Investigator: BMS;Non-Financial Interests, Personal, Principal Investigator: MSD;Non-Financial Interests, Personal, Principal Investigator: Pfizer;Non-Financial Interests, Personal, Principal Investigator: Lytix Pharma;Non-Financial Interests, Personal, Principal Investigator: Eisai;Non-Financial Interests, Personal, Principal Investigator: AstraZeneca;Non-Financial Interests, Personal, Principal Investigator: Tesaro;Non-Financial Interests, Personal, Principal Investigator: Chugai;Non-Financial Interests, Personal, Principal Investigator: Ose Immunotherapeutics;Non-Financial Interests, Personal, Principal Investigator: Sotio;Non-Financial Interests, Personal, Principal Investigator: Molecular Partners;Non-Financial Interests, Personal, Principal Investigator: IMCheck;Non-Financial Interests, Personal, Principal Investigator: Pierre Fabre;Non-Financial Interests, Personal, Principal Investigator: Adlai Nortye;Financial Interests, Personal, Stocks/Shares: Pegascy SAS;Financial Interests, Personal, Stocks/Shares: Centessa Pharmaceuticals;Financial Interests, Personal, Stocks/Shares: HiFiBio;Financial Interests, Personal, Stocks/Shares: Shattuck Labs;Financial Interests, Institutional, Research Grant: Merus;Financial Interests, Institutional, Research Grant: BMS;Financial Interests, Institutional, Research Grant: Boehringer Ingelheim;Financial Interests, Institutional, Research Grant: Transgene;Financial Interests, Institutional, Research Grant: Fondation MSD Avenir;Financial Interests, Institutional, Research Grant: Sanofi. All other authors have declared no conflicts of interest.

Hydration is needed before and after cisplatin infusion for reducing the risk of nephrotoxicity. Even though there is no standard regimen, patients receive mostly intravenous hydration before and after cisplatin leading hospitalization during at least one night. Since the feasibility has been published, oral hydration after cisplatin was implemented in our practice. The safety of this new way of hydration needs to be assessed in clinical practice. We collected medical records from patients treated by cisplatin for lung cancer in our unit between 2010 and 2016. We retrospectively analyzed the incidence of cisplatin induced nephrotoxicity between after and before the change of hydration regimen. Our patient cohort included 241 patients hydrated by intravenous regimen (IV/IV group) and 276 patient hydrated by intravenous and oral regimen (IV/PO group). Grade ≥ 1 nephrotoxicity occurred in 39.4 and 25.7% in the IV/IV and IV/PO groups respectively (p = 0.001). Age over 70 at baseline was a predictive factor for nephrotoxicity, but not estimated glomerular filtration rate nor cisplatin-associated drugs. After a multivariate analysis, age remained a predictive factor for nephrotoxicity and IV/PO hydration associated with a decrease in nephrotoxic risk. The implementation of oral hydration in our practice was not associated with an increase in nephrotoxicity. Our observation based on large data from clinical practice shows that oral hydration after cisplatin is safe.

Neurofibromas involving airways are rare and their management is usually surgical. Herein, we report the case of an endotracheal polypoid neurofibroma successfully treated by multimodal interventional bronchoscopy and cryotherapy.