Oncodrivers in Malignant Pleural Effusions Associated With Non-small Cell Lung Cancer: A Prospective Study.

Study Overview
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Brief Summary
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Oncological treatment of patients with disseminated non-small cell lung cancer (NSCLC) is depending on the status of programmed death-ligand 1 (PD-L1), anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR), so called oncodrivers. These can be measured in pleural fluid, but the prevalence is uncertain. In a prospective study, the research team aim to measure PD-L1, ALK and EGFR in patients with pleural fluid cytology positive for NSCLC to report the prevalence. Also, the study will investigate if the chance of obtaining oncodriver status is depending on the volume analysed and how the lack of oncodrivers influence the following work-up.

Detailed Description
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The study is a prospective, non-randomized, cohort study of patients with pleural effusion. Participants will be recruited from patients referred to the Pleura Clinic or admitted at the ward at the Department of Respiratory Medicine, Næstved Hospital, Næstved or at the Department of Respiratory Medicine, Zealand University Hospital, Roskilde, which is the two regional centres for workup of pleural effusions. Patients will be referred from either general practice or other hospital departments. Pleural fluids with cytology positive for NSCLC will be tested for oncodrivers (for squamous cell carcinomas (SCC): PD-L1, for adenocarcinomas (AC): PD-L1, ALK and EGFR). Follow-up will be 8 weeks after inclusion.

Official Title
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The Prevalence of Oncodrivers in Malignant Pleural Effusions Associated With Non-small Cell Lung Cancer: A Prospective Study.

Conditions
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Malignant Pleural Effusion, Non-small Cell Lung Cancer

Intervention / Treatment
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* Diagnostic Test: meassurement of PD-L1, ALK, EGFR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Pleural effusion known or suspected of association with NSCLC (pleural fluid cytology positive for cells from NSCLC) Patients must be able to give informed consent Exclusion Criteria: Full oncodriver status measured in any pleural fluid in current work-up Inability to understand written or spoken Danish.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: prospective, non-randomized, cohort study
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: meassurement of PD-L1, ALK, EGFR|PD-L1 test will be performed on cell-blocks using PD-L1 antibodies 22C3 and staining platform Dako Omnis (Agilent, Glostrup -Denmark). ALK test will be performed on cell-blocks using staining platform Dako Omnis (Agilent, Glostrup- Denmark) and ALK antibodies Origene clone: OT1A4. Sample quality is assessed as for PD-L1. EGFR mutation analysis will be performed as follows: after tumor content evaluation of hematoxylin and eosin stained slides, relevant regions are macrodissected and subjected to a standard genomic DNA extraction procedure using the GeneRead DNA FFPE Kit (Qiagen). Samples will be analysed using the GeneRead QIAact Actionable Insights Tumor Panel (Qiagen)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of oncodriver status | Prevalence of oncodriver status (for squamous cell carcinomas (SCC): PD-L1, for adenocarcinomas (AC): PD-L1, ALK and EGFR) in pleural fluid in patients with cytology positive for pulmonary NSCLC | assessed at 8 weeks follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of adequate and inadequate pleural fluid specimens |  | assessed at 8-week follow-up | 
| Amounts of pleural fluid sent for analysis | Meassured in mL. | assessed at 8-week follow-up | 
| Correlation between amounts of pleural fluid sent to the pathologist and the chance of obtaining oncodriver status |  | assessed at 8-week follow-up | 
| Number and type of additional diagnostic interventions including additional thoracentesis and cytological or histological biopsies |  | assessed at 8-week follow-up | 
| Prevalence of oncodriver status in additional diagnostic interventions |  | assessed at 8-week follow-up | 
| - Correlation between oncodriver status obtained in pleural fluid specimens and cytological or histological biopsies |  | assessed at 8-week follow-up | 
| - Proportion of work-ups where the lack of obtained oncodriver status in pleural fluid specimens leads to additional diagnostic interventions including additional thoracentesis and cytological or histological biopsies |  | assessed at 8-week follow-up | 
| - Proportion of work-ups where full oncodriver-status was obtained at the second thoracentesis |  | assessed at 8-week follow-up | 
| - Proportion of patients with pleural fluid cytology negative of NSCLC, who is diagnosed with NSCLC. |  | assessed at 8-week follow-up | 
| Patient assessed pain during thoracentesis | assessed by a questionnaire containing a VAS (Visual Analogue Scale, scale 0-10, 0 being no pain, 10 being the worse pain) | at day 1, 2 minutes after thoracentesis | 
| Proportion of patients experiencing pneumothorax |  | assessed at day 1, 10 minutes after thoracentesis and 8-week follow-up by evaluating the patient file | 
| Proportion of patients experiencing bleeding |  | assessed at day 1, 10 minutes after thoracentesis and 8-week follow-up | 
| Proportion of complications leading to admission | assessed by evaluating the patient file | assessed at 8-week follow-up |