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opencc-by-4.0Apr 2020View details →

Lung ultrasonography features and risk stratification in 80 patients with COVID-19: a prospective observational cohort study

Background Point-of-care lung ultrasound (LUS) is a promising and pragmatic risk stratification tool in COVID-19. This study describes and compares early LUS characteristics across of range of clinical outcomes. Method Prospective observational study of PCR-confirmed COVID-19 patients in the emergency department (ED) of Lausanne University Hospital. A trained physician recorded LUS images using a standardized protocol. Two experts retrospectively reviewed images blinded to patient outcome. We describe and compare early LUS findings (acquired within 24hours of presentation at the ED) between patient groups based on their outcome at 7-days after inclusion:  1) self-resolving outpatients, 2) hospitalised and 3) intubated/death. The LUS score was used to discriminate between groups. Findings Between March 6 and April 3 2020, we included 80 patients (18 outpatients, 41 hospitalized and 21 intubated/dead). 73 patients (91%) had abnormal LUS (72% outpatients, 95% hospitalised and 100% intubated/death; p=0.004). The proportion of involved zones was lower in outpatients compared with other groups (median  30% [IQR 0-40%], 44% [33-70%] and 70% [50-88%], p<0.001). Predominant abnormal patterns were bilateral and multifocal spread thickening of the pleura with pleural line irregularities (77%), confluent B lines (66%) and pathologic B lines (55%). Posterior inferior zones were more often affected. Median LUS score had a good level of discrimination between outpatients and others with area under the ROC of 0.80 (95% CI 0.66-0.95). Interpretation Systematic LUS is a reliable, cheap and easy-to-use triage tool for the early stratification of risk in COVID-19 patients presenting at emergency departments. Funding Leenaards Foundation

opencc-zeroApr 2016View details →

MicroRNA Panel Predicts Lung Adenocarcinoma in Patients Presenting with Ground-Glass Nodules

MicroRNA (miRNA) expression is correlated with tumor histology, differentiation, invasiveness and treatment outcome. We aimed to identify miRNAs whose differential expression might enable early diagnosis of lung adenocarcinoma in patients presenting with ground-glass nodules (GGNs). To identify potential miRNAs of interest, we analyzed the miRNA expression profile of tumor and adjacent non para-tumor tissue in 3 participants by next-generation sequencing (NGS). We then assessed the expression levels of the miRNAs of interest in 73 lung adenocarcinoma presenting with GGNs with matched adjacent non-tumor tissue by quantitative real-time polymerase chain reaction (qRT-PCR). Target genes of our selected miRNA panel were predicted using Miranda with default parameters. Twenty-three miRNAs showed differential expression between tumor and adjacent non-tumor tissue by NGS. Five miRNAs exhibited higher expression in tumor tissue compared to adjacent non-tumor tissue (P＜0.05), eighteen miRNAs demonstrated lower expression in tumor tissue versus adjacent non-tumor tissue (P＜0.05). When qRT-PCR was performed for the 23 miRNAs identified by NGS in the pilot stage, seven were found to have statistically significant expression in tumor versus adjacent non-tumor tissue (P＜0.05). The predicted targets of our miRNAs of interest are frequently associated with cancer signaling pathways. We developed a miRNA panel that could potential predict the presence of lung adenocarcinoma in patients presenting with GGNs.

opencc-by-4.0Jan 2024View details →

Single-cell RNA-seq profiles of lung adenocarcinoma patients and tumor-bearing mice

single-cell RNA sequencing (scRNA-seq) profiles from eight patients with lung adenocarcinoma (LUAD) and four samples of tumor tissues from tumor bearing mice were performed. By integrating other scRNA-seq data and clinical information, we identified activated adaptive immune responses in older patients, reflected by enriched dysfunctional T cell signature scores and immune checkpoint molecules. Our study shows increased efficacy of immune checkpoint blockade therapy in older patients, addressing the prominent role of age when considering immunotherapy.

opencc-by-4.0Feb 2022View details →

Bevacizumab plus erlotinib versus erlotinib alone as first line treatment of patients with EGFR-mutated advanced nonsquamous non-small cell lung cancer. BEVacizumab plus ERLotinib studY (BEVERLY): an academic, multicenter, randomised phase III trial.

Background. Adding bevacizumab to erlotinib prolonged PFS of patients with EGFR-mutated advanced NSCLC in the Japanese NEJ026 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized phase III trial of bevacizumab plus erlotinib versus erlotinib alone as first-line treatment of advanced EGFR-mutated NSCLC. Methods. Eligible patients were randomized 1:1 to erlotinib (150mg daily) plus bevacizumab (15mg/kg iv q3w) or erlotinib alone, until disease progression or unacceptable toxicity. Center, ECOG PS and type of mutation (ex19 deletion vs ex21 L858R vs others) were stratification variables. Investigator-assessed PFS (IA-PFS) and blinded-independent centrally-reviewed PFS (BICR-PFS) were co-primary endpoints. With 80% power in detecting a 0·60 HR and 2–sided α error 0·05, 126 events out of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17. Findings. From Apr 11, 2016 to Feb 27, 2019, 160 pts were randomized to erlotinib pus bevacizumab (80) or erlotinib alone (80). Baseline characteristics were balanced between arms; 34 (42·5%) patients in erlotinib plus bevacizumab arm and 43 (53·8%) in erlotinib arm were former or current smokers. At a median follow-up of 36·3 months, 140 PFS events (87·5%) were reported, 68 with erlotinib plus bevacizumab and 72 with erlotinib. Median IA-PFS was 15·4 months (95% CI 12·2–18·6) with erlotinib plus bevacizumab and 9·6 months (95% CI 8·2–10·6) with erlotinib (HR 0·66; 95%CI: 0·47–0·92). BICR-PFS analysis confirmed this result. A significant interaction with treatment effect was found for smoking habit (P=0·0323): former or current smokers receiving erlotinib plus bevacizumab had a longer PFS (16·9 months [95% CI 10·2–21·8] versus 8·8 months [95% CI 5·6–9·6]) than those receiving erlotinib alone. Hypertension (grade≥3: 24% vs 5%), skin rash (grade≥3: 31% vs 14%), thromboembolic events (any grade: 11% vs 4%), and proteinuria (any grade: 23% vs 6%) were more frequent with the combination treatment. Interpretation. The addition of bevacizumab to first-line erlotinib significantly prolonged PFS in Italian patients with EGFR-mutated NSCLC, without unexpected safety issues.

opencc-by-4.0Jun 2024View details →

Real-world comprehensive genomic and immune profiling reveals distinct age- and sex-based genomic and immune landscapes in tumors of patients with non-small cell lung cancer

Wallen ZD, Ko H, Nesline MK, Hastings SB, Strickland KC, Previs RA, Zhang S, Pabla S, Conroy J, Jackson JB, Saini KS, Jensen TJ, Eisenberg M, Caveney B, Sathyan P, Severson EA, Ramkissoon SH. Real-world comprehensive genomic and immune profiling reveals distinct age- and sex-based genomic and immune landscapes in tumors of patients with non-small cell lung cancer. Front Immunol. 2024 Jun 21;15:1413956. doi: <a href="https://doi.org/10.3389/fimmu.2024.1413956">10.3389/fimmu.2024.1413956</a>. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/38975340/">38975340</a>; PMCID: <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11224431/">PMC11224431</a>. ABSTRACT Younger patients with non-small cell lung cancer (NSCLC) (<50 years) represent a significant patient population with distinct clinicopathological features and enriched targetable genomic alterations compared to older patients. However, previous studies of younger NSCLC suffer from inconsistent findings, few studies have incorporated sex into their analyses, and studies targeting age-related differences in the tumor immune microenvironment are lacking. We performed a retrospective analysis of 8,230 patients with NSCLC, comparing genomic alterations and immunogenic markers of younger and older patients while also considering differences between male and female patients. We defined older patients as those ≥65 years and used a 5-year sliding threshold from <45 to <65 years to define various groups of younger patients. Additionally, in an independent cohort of patients with NSCLC, we use our observations to inform testing of the combinatorial effect of age and sex on survival of patients given immunotherapy with or without chemotherapy. We observed distinct genomic and immune microenvironment profiles for tumors of younger patients compared to tumors of older patients. Younger patient tumors were enriched in clinically relevant genomic alterations and had gene expression patterns indicative of reduced immune system activation, which was most evident when analyzing male patients. Further, we found younger male patients treated with immunotherapy alone had significantly worse survival compared to male patients ≥65 years, while the addition of chemotherapy reduced this disparity. Contrarily, we found younger female patients had significantly better survival compared to female patients ≥65 years when treated with immunotherapy plus chemotherapy, while treatment with immunotherapy alone resulted in similar outcomes. These results show the value of comprehensive genomic and immune profiling (CGIP) for informing clinical treatment of younger patients with NSCLC and provides support for broader coverage of CGIP for younger patients with advanced NSCLC. DATA AVAILABILITY:  De-identified, individual-level patient data, genomic variants, and individual immune gene expression data used in the manuscript can be found in this repository (https://zenodo.org/record/11396552). An R markdown file with R code used to perform the analyses and generate figures is also provided in the repository along with the data. All versions of software used are provided in the Methods section of the manuscript. Raw sequencing data were derived from routine clinical testing of real-world patients and cannot be shared publicly. Data for immune gene expression signatures are not publicly available due to a non‑provisional patent filing covering the methods used to generate and analyze these data but are available from the corresponding author on reasonable request.

opencc-by-4.0Dec 2022View details →

Processed counts data of cfMeDIP-seq profiles of small cell lung cancer patients

R objects of cfMeDIP-seq profiles of small cell lung cancer patient cfDNA, peripheral blood leukocytes, non-cancer control patients cfDNA, and CDX tumour tissue. The data are whole-genome across 300bp windows after removing ENCODE-blacklisted regions. The data also includes MeDEStrand-converted MeDIP data for peripheral blood leukocytes

Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin)

ClinicalTrials.gov study NCT01524783. IPD Sharing: YES. Countries: 25. Publications: 5.

Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer

ClinicalTrials.gov study NCT02323126. IPD Sharing: YES. Countries: 8. Publications: 1.

LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

ClinicalTrials.gov study NCT01828099. IPD Sharing: YES. Countries: 29. Publications: 2.

restrictedIPD-UNDECIDEDFeb 2026View details →

Evaluation of Lung Clearance Index in Cystic Fibrosis (CF) Patients, Infected With P.Aeruginosa

ClinicalTrials.gov study NCT02248922. IPD Sharing: UNDECIDED. Countries: 1. Publications: 1.

The Effect of Dupilumab on Lung Inflammation and Related Changes in Airway Volumes Detectable by Functional Respiratory Imaging in Patients With Moderate-severe Asthma

ClinicalTrials.gov study NCT04400318. IPD Sharing: YES. Countries: 13. Publications: 2.

LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

ClinicalTrials.gov study NCT01685138. IPD Sharing: YES. Countries: 18. Publications: 2.

Pembrolizumab in Patients With Non-Small Cell Lung Cancer and a Performance Status 2

ClinicalTrials.gov study NCT02733159. IPD Sharing: YES. Countries: 1. Publications: 1.

Study of Safety and Efficacy of EGFR-TKI EGF816 in Combination With cMET Inhibitor INC280 in Adult Patients With EGFR Mutated Non Small Cell Lung Cancer.

ClinicalTrials.gov study NCT02335944. IPD Sharing: YES. Countries: 11. Publications: 2.

Study of Oral cMET Inhibitor INC280 in Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC) (Geometry Mono-1)

ClinicalTrials.gov study NCT02414139. IPD Sharing: YES. Countries: 20. Publications: 3.

opencc-by-4.0Nov 2023View details →

Multi-breath 4DCT images of lung cancer patients

Multi-breath 4DCT images of six non-small cell lung cancer (NSCLC) patients.Breathing motion has been transferred across longitudinal imaging to generate new 4DCT images sampling five consecutive breaths.This dataset is the result of processing six subjects selected from the 4D-Lung dataset published in The Cancer Imaging Archive: <a href="https://doi.org/10.7937/K9/TCIA.2016.ELN8YGLE">https://doi.org/10.7937/K9/TCIA.2016.ELN8YGLE </a>Hugo et al. (2016).Data generated within the project "New concept for adaptive real time tumour tracking" funded by the Swiss National Science Foundation (SNSF) under grant agreement 200021_185082: <a href="https://data.snf.ch/grants/grant/185082">https://data.snf.ch/grants/grant/185082</a>

A detailed ultrastructural examination of lung cryobiopsy samples from a COVID-19 patient case series – Data set 12

We investigated six cryobiopsy samples from six deceased patients (patients C03 to C08 from Barisione et al. 2020 <a href="https://doi.org/10.1007/s00428-020-02934-1">doi.org/10.1007/s00428-020-02934-1</a>) by using thin section electron microscopy (Cortese et al. 2022 <a href="http://doi.org/10.1007/s00428-022-03308-5">doi.org/10.1007/s00428-022-03308-5</a>). A detailed description of the methods and the data set is provided in the download container. Data set 12 contains stitched image montages of thin sections (selected areas) through the lung of patients C04 and C07 which were acquired by scanning electron microscopy. The images show alveolae with various degree of epithelial damage.

A detailed ultrastructural examination of lung cryobiopsy samples from a COVID-19 patient case series – Data set 11

We investigated six cryobiopsy samples from six deceased patients (patients C03 to C08 from Barisione et al. 2020 <a href="https://doi.org/10.1007/s00428-020-02934-1">doi.org/10.1007/s00428-020-02934-1</a>) by using thin section electron microscopy (Cortese et al. 2022 <a href="http://doi.org/10.1007/s00428-022-03308-5">doi.org/10.1007/s00428-022-03308-5</a>). A detailed description of the methods and the data set is provided in the download container. Data set 11 contains a stitched image montage of a thin section (selected area) through the lung of patient C05 which was acquired by scanning electron microscopy. The image shows a lung area with a dissolved alveolar architecture and a massive type-2-cell hyperplasia.

A detailed ultrastructural examination of lung cryobiopsy samples from a COVID-19 patient case series – Data set 10

We investigated six cryobiopsy samples from six deceased patients (patients C03 to C08 from Barisione et al. 2020 <a href="https://doi.org/10.1007/s00428-020-02934-1">doi.org/10.1007/s00428-020-02934-1</a>) by using thin section electron microscopy (Cortese et al. 2022 <a href="http://doi.org/10.1007/s00428-022-03308-5">doi.org/10.1007/s00428-022-03308-5</a>). A detailed description of the methods and the data set is provided in the download container. Data set 10 contains stitched image montages of thin sections (selected areas) through the lung of patient C08 which were acquired by transmission electron microscopy. Cells, infected with SARS-CoV-2 particles, are shown in overview (A, C) and detail (B, C).

A detailed ultrastructural examination of lung cryobiopsy samples from a COVID-19 patient case series – Data set 14

We investigated six cryobiopsy samples from six deceased patients (patients C03 to C08 from Barisione et al. 2020 <a href="https://doi.org/10.1007/s00428-020-02934-1">doi.org/10.1007/s00428-020-02934-1</a>) by using thin section electron microscopy (Cortese et al. 2022 <a href="http://doi.org/10.1007/s00428-022-03308-5">doi.org/10.1007/s00428-022-03308-5</a>). A detailed description of the methods and the data set is provided in the download container. Data set 14 contains stitched image montages of a thin section through the lung of patient C04 which were acquired by scanning electron microscopy. The file “Data_set_14.tif” contains a montage of the entire thin section while the other files contain selected areas of the section recorded at higher resolution.