Evaluation of Multiple Biomarkers in Serum and Pleural Fluid to Estimate the Probability of Cancer in Patients Presenting With an Undiagnosed Pleural Effusion
Approximately 1.6 million cases of pleural effusion are seen in the US per year, with
~210,000 of those cases due to underlying malignancy. Pleural fluids have traditionally
been divided into two types: transudative and exudative. The most common causes of
transudative pleural effusion are congestive heart failure and cirrhosis. Common causes of
exudative pleural effusion include malignancy, pneumonia, pulmonary embolism and viral
infection. One study found that 42% of all exudative effusions were due to malignancy, and
another found that malignancy was the underlying cause of 24% of all effusions.
Differential diagnosis of the various causes of effusions is complex and includes gross
appearance of the pleural fluid (PF), differential cell count, cytology, glucose and LDH
levels, and sometimes adenosine deaminase (ADA) levels. In addition, spiral CT scans,
bronchoscopy, thoracoscopy, needle biopsy of the pleura, and video assisted thoracoscopy
(VATS) are all utilized to determine the underlying cause of pleural fluid accumulation.
These procedures are expensive and may be traumatic to patients. In approximately 20% of
patients presenting with pleural fluid accumulation, no underlying cause will be
established. Despite promising results published in peer-reviewed journals over the last
two decades, serum biomarkers have not gained acceptance as a standard of care in the
management of patients with lung cancer, mesothelioma, or pleural effusion. The purpose of
this clinical trial is to evaluate the ability of various biomarkers measured in serum
and/or pleural fluids to estimate the risk of finding cancer in patients with undiagnosed
pleural effusions. An algorithm for prediction of the risk of finding cancer in the patient
using an optimal combination of markers will be developed, and patients will be categorized
as having a low, moderate, or high risk of finding cancer that might be used to more
effectively triage patients. For example, a high risk of cancer may be used to justify more
invasive or expensive procedures, such as spiral CT scans and thoracoscopy.
This is a prospective, multi-center, double-blind, statistically powered clinical trial that
will enroll patients scheduled to undergo a procedure for removal of fluid from a pleural
effusion (i.e. thoracentesis, thoracoscopy, image guided thoracentesis, thoracotomy, chest
tube placement, Pleurex® catheter insertion, etc.).
The primary objective of the study is to evaluate the ability of multiple biomarkers in
serum and/or pleural fluid to estimate the risk of finding cancer in subjects presenting
with an undiagnosed pleural effusion (i.e. unknown origin).
The secondary objective of the study is to compare the ability of multiple biomarkers in
serum and/or pleural fluid combined with pleural fluid cytology and other laboratory results
to the use of the multiple biomarkers alone to estimate the risk of finding cancer in
subjects presenting with an undiagnosed pleural effusion.
The research objectives of the study are the evaluation of the utility of multiple
biomarkers in serum and/or pleural fluid to predict the tissue of origin in subjects with
cancer who presented with an undiagnosed pleural effusion and comparison of these results to
pleural fluid cytology. Correlation of the biomarker levels in the serum and pleural fluid
will be evaluated as well.
Observational Model: Cohort, Time Perspective: Prospective
Jeffrey Allard, PhD
Fujirebio Diagnostics, Inc.
United States: Food and Drug Administration
FDI-02 Pleural Effusion Study
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