Biomarker Identifies Brain Metastases in Lung Cancer Patients

Lara C. Pullen, PhD

November 20, 2013

CHICAGO — Levels of the serum biomarker S100B, in combination with S100B antibody levels, can be used to accurately identify brain metastases in patients with lung cancer, according to a new study.

The use of S100B as a biomarker for brain metastases might decrease the cost of imaging in this patient population, said Humberto Choi, MD, from the Department of Pulmonary, Allergy and Critical Care Medicine at the Cleveland Clinic. However, he did acknowledge "that our numbers are low."

Dr. Choi presented results from the longitudinal prospective study here at CHEST 2013.

S100B is a protein found in the brain, muscle, and fat. It is synthesized by astrocytes in the brain and released into the bloodstream when the blood–brain barrier is disrupted. Because the growth of metastatic lesions in the brain compromises the integrity of the blood–brain barrier, investigators postulated that serum levels of S100B could be a possible biomarker of brain metastases.

In addition, previous studies have demonstrated that autoantibodies are produced after lengthy exposure to S100B. This finding led Dr. Choi and colleagues to hypothesize that S100B antibody levels might be useful to distinguish long-term and sustained blood–brain barrier damage associated with cerebrovascular damage from the blood–brain barrier disruption that is characteristic of brain metastasis.

The study involved 111 adults seen at the Cleveland Clinic from 2010 to 2012 with a new or untreated diagnosis of lung cancer at any stage. Patients with and without neurologic symptoms were included.

The investigators found that serum levels of S100B were highly sensitive for identifying lung cancer patients with brain metastases. When they combined the levels of S100B with levels of the antibody to S100B, they were able to increase specificity without loss of sensitivity.

When they included clinical information, such as staging before brain imaging, they were able to increase accuracy.

The biomarker assay had 100% sensitivity and 43.3% specificity in the 33 patients who were initially identified as having stage I or II brain metastasis.

Table. Patients Classified as Having Stage I or II Brain Metastasis Before Brain Imaging

S100B Serum Levels Brain Metastasis, n No Metastasis, n
S100B ≥0.05 plus S100B antibodies <2.0 3 17
Other combinations 0 13


On the basis of these results, 39.3% of these patients would not require brain imaging for staging.

Dr. Choi's team extrapolated the study data to the population in the United States as a whole to illustrate the potential cost savings of a S100B biomarker assay.

They estimated that in 2013 there would be 228,000 cases of lung cancer, 34,200 (15%) of which would likely be localized disease. The biomarker assay would, theoretically, make it possible to forgo imaging in more than 13,000 patients in the localized disease group. Assuming a cost of $3300 per MRI, this would translate into a savings of $44,015,400.

"It was a very good presentation," said Michael A. Jantz, MD, FCCP, from the University of Florida Health in Gainesville. "It looks like the numbers were pretty good to exclude metastases at the early stages."

The reception from the audience was also positive, with one audience member calling the S100B biomarker assay "an alternative way to stage patients."

Dr. Choi has disclosed no relevant financial relationships. One of his coauthors, Damir Janigro, PhD, from the Cleveland Clinic, developed the S100B test and will receive payments related to this technology.

CHEST 2013: American College of Chest Physicians Annual Meeting: Abstract. Presented August 27, 2013.


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