Advancing real-world research in thoracic malignancies: learnings from the international I-O Optimise initiative.

In recent years, the thoracic malignancies treatment landscape has become more complex with the emergence of novel targeted and immunotherapy-based treatments. Although beneficial to patients and physicians, this fast-paced therapeutic evolution has increased the complexity of clinical decision-making and amplified the importance of real-world evidence to support data from randomized controlled trials. The international I-O Optimise initiative was established in 2016 to provide real-world insights into the thoracic malignancies treatment landscape, and has since collaborated with 14 data sources across Europe and Canada, allowing access to data from ~ 500,000 patients with non-small-cell lung cancer, small-cell lung cancer, and malignant pleural mesothelioma.

Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine.

Purpose: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy.

Methods: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included.

Patient characteristics, treatment patterns, and survival outcomes for patients with malignant pleural mesothelioma in Denmark between 2011 and 2018: a nationwide population-based cohort study.

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with poor prognosis and limited treatment options. Immunotherapy shows potential for improved outcomes; however, real-world evidence on its use will take time to accumulate. This study examined patient characteristics, treatment patterns, overall survival (OS), and predictors of mortality among patients diagnosed with MPM in Denmark prior to the introduction of newer treatments.

UV1 telomerase vaccine with ipilimumab and nivolumab as second line treatment for pleural mesothelioma - A phase II randomised trial.

Purpose: The NIPU-trial investigates the effect of adding the telomerase vaccine UV1 to treatment with ipilimumab and nivolumab for patients with pleural mesothelioma (PM).

Methods: In this phase 2 open-label trial, patients with PM progressing after first-line chemotherapy were randomised to receive ipilimumab and nivolumab alone (arm B) or combined with UV1 (arm A). The primary endpoint was progression-free survival (PFS) as determined by BICR.

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Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumour and a cause of hydrocele. This case report concerns a 26-year-old male with hydrocele treated with left hydrocelectomy. Histopathology revealed MTVT, and left radical orchiectomy was performed followed by chemotherapy.

New pathogenic germline variants identified in mesothelioma.

Background: Mesothelioma (MM) is associated with asbestos exposure, tumor heterogeneity and aggressive clinical behavior. Identification of germline pathogenic variants (PVs) in mesothelioma is relevant for identifying potential actionable targets and genetic counseling.

Methods: 44 patients underwent whole exome sequencing (WES) or whole genome sequencing (WGS).

Correlation of MET-Receptor Overexpression with MET Gene Amplification and Patient Outcome in Malignant Mesothelioma.

Thanks to clinically newly introduced inhibitors of the mesenchymal-epithelial transition (MET) receptor tyrosine-kinase, MET-gene copy number gain/amplification (MET-GCNG/GA) and increased expression of the MET protein are considered very promising therapeutic targets in lung cancer and other malignancies. However, to which extent these MET alterations occur in malignant mesothelioma (MM) remains unclear. Thus, we investigated by well-established immunohistochemistry and fluorescence in situ hybridization methods, the frequency of these alterations in specimens from 155 consecutive MMs of different subtypes obtained from pleural or peritoneal biopsies and pleurectomies.

Initial treatment and survival in Danish patients diagnosed with non-small-cell lung cancer (2005-2015): SCAN-LEAF study.

To describe initial treatment patterns and survival of patients diagnosed with non-small-cell lung cancer (NSCLC) in Denmark, before immune checkpoint inhibitor and later-generation tyrosine kinase inhibitor use. Adults diagnosed with incident NSCLC (2005-2015; follow-up: 2016). Initial treatments and overall survival (OS) are reported.

Intracranial effect of osimertinib in relapsed -mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study.

Introduction: Osimertinib is effective for relapsed T790M-positive patients with brain metastases. The high brain permeability suggests that also such patients without T790M could benefit. Therefore, we evaluated the effect of osimertinib on brain metastases in both T790M-positive and -negative patients.

Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial.

Background: Nintedanib targets VEGF receptors 1-3, PDGF receptors α and β, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma.

Methods: This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world.

Very Early Response Evaluation by PET/MR in Patients with Lung Cancer-Timing and Feasibility.

With the increasing number of therapy options available for patients with lung cancer, early response evaluation is needed. We performed this pilot study to assess the feasibility of early, repeated Positron emission tomography-magnetic resonance (PET/MR), the impact of timing and the capability for response prediction in lung tumors during chemotherapy. Patients with stage IV non-small cell lung cancer referred for chemotherapy were prospectively recruited.

18F-FDG PET/CT Findings in Disseminated Genital Herpes in an Immunocompetent Patient With Anaplastic Lymphoma Kinase Rearranged Advanced Nonsmall Cell Lung Cancer.

We present the PET/CT findings of extensive disseminated genital herpes simplex virus infection in a 29-year-old woman known with disseminated anaplastic lymphoma kinase-mutated nonsmall lung cancer. PET/CT revealed extensive involvement of the outer and inner genitalia, multiple lymph nodes extending from the porta hepatis to the groins, and involvement of the liver. Disseminated herpes simplex virus infection is well described in neonates and immunocompromised individuals but very rare in immunocompetent adults as was the case with this patient.

Concomitant driver mutations in advanced -mutated non-small-cell lung cancer and their impact on erlotinib treatment.

Background: Patients with -mutated non-small-cell lung cancer benefit from EGFR tyrosine kinase inhibitors (TKIs) like erlotinib. However, the efficacy may be impaired by driver mutations in other genes.

Methods: Five hundred and fourteen consecutive patients with NSCLC of all stages were tested for -mutations by cobas® EGFR Mutation Test.

Molecular prediction of adjuvant cisplatin efficacy in Non-Small Cell Lung Cancer (NSCLC)-validation in two independent cohorts.

Introduction: Effective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts are presented.

Methods: The profiles are correlations between in vitro sensitivity to cisplatin and vinorelbine and baseline mRNA expression of the 60 cell lines in the National Cancer Institute panel.

Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial.

Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression.

Implementation of lung cancer CT screening in the Nordic countries.

Introduction: We review the current knowledge of CT screening for lung cancer and present an expert-based, joint protocol for the proper implementation of screening in the Nordic countries.

Materials And Methods: Experts representing all the Nordic countries performed literature review and concensus for a joint protocol for lung cancer screening.

Results And Discussion: Areas of concern and caution are presented and discussed.

High RRM1 Expression Is Associated with Adverse Outcome in Patients with Cisplatin/Vinorelbine-treated Malignant Pleural Mesothelioma.

Background/aim: A possible predictive impact of ribonucleotide-reductase subunit-1 (RRM1) on vinorelbine efficacy in non-small cell lung cancer (NSCLC) has been previously reported. The present study aimed to further explore this finding in malignant pleural mesothelioma (MPM).

Materials And Methods: Seventy-one patients with MPM receiving first-line chemotherapy with cisplatin-vinorelbine (CiV group, n=54) or carboplatin-pemetrexed (CaP group, n=17) were included.

Platinum-Vinorelbine Induction Chemotherapy plus Bevacizumab With and Without Pemetrexed Switch Maintenance in Advanced NSCLC.

Background: Little information is available until today regarding the effect of platinum-doublet chemotherapy with bevacizumab followed by pemetrexed as a sole maintenance treatment. Original data concerns different induction regimens plus bevacizumab with bevacizumab maintenance to progression in advanced non-squamous non-small cell lung cancer (NSCLC).

Patients And Methods: Two consecutive groups of patients with advanced non-squamous NSCLC received carboplatin, vinorelbine and bevacizumab for four cycles.

Methylation-associated Silencing of microRNA-126 and its Host Gene EGFL7 in Malignant Pleural Mesothelioma.

Background/aim: We recently reported that miR-126 is down-regulated in malignant pleural mesothelioma (MPM) and can be combined into a 4-microRNA-classifier that can accurately diagnose MPM with high sensitivity and specificity. Herein we analyzed the epigenetic regulation of miR-126 and its host gene EGF-like domain, multiple 7 (EGFL7).

Materials And Methods: Resected formalin-fixed paraffin-embedded MPM tissues from 29 patients, 14 patient-matched non-neoplastic pleura (NNP) specimens, 5 MPM diagnostic biopsies (DB), and 5 samples of pneumothorax-induced benign reactive mesothelial proliferation (PTHX) were analyzed.