News | October 22,
2013 | Lung Cancer
A blood test that detects a combination of proteins can distinguish between
early lung cancer and noncancerous lung nodules, according to a study published
in Science Translational Medicine. The two types of nodules are currently
difficult to distinguish using imaging. The test showed a 90% negative
predictive value in a study of 104 patient samples from three clinical sites.
Further validation on 37 samples from a single site showed a 94% negative
predictive value.
This molecular test may complement the current tools used
by clinicians to diagnose early-stage lung cancer.
The early lung cancer detection test is being developed
by Seattle-based molecular diagnostic company Integrated Diagnostics (Indi).
The test detects the levels of 13 proteins in a patient’s blood sample and
could prevent unnecessary biopsies of lung nodules detected by CT scans.
“These studies suggest that Indi’s technology is capable
of detecting the molecular signature of lung cancer by measuring the presence
of multiple proteins in a patient’s blood,” said senior author Paul Kearney,
PhD, president and chief science officer of Integrated Diagnostics, in a
released statement.
The researchers used a systems biology approach,
screening 371 blood-based proteins on 143 patient samples with either benign or
stage 1A lung cancer that were matched for nodule size, age, gender, and
clinical site.
Multiple reaction monitoring (MRM) mass spectrometry is
used to analyze the relative concentrations on biomarkers. The technology
allows simultaneous analysis of many protein levels.
Further analysis to understand the role of these
biomarker proteins showed that all 13 are likely regulated by four
transcription factors that bind to the regulatory elements of the 13 genes that
encode the proteins. All four transcription factors have been associated with
lung inflammation and lung cancer, as well as oxidative stress pathways.
The validation using 104 patient samples showed a test
sensitivity of 71% and specificity of 44%. The study researchers assumed that
the rate of cancer prevalence was 15%. At the same cancer prevalence rate, the
sensitivity was 82% and the specificity was 66% in the discovery cohort of 143
samples.
The protein levels were found to be independent of known
risk factors for pulmonary nodules: the size of the nodule detected, history of
smoking, and age.
According to Kearney and fellow study authors, one-fifth
of patients with detectable lung nodules who undergo biopsy or surgery actually
have a malignant nodule. Therefore, a reliable test that can discriminate
between a benign lung mass and a cancerous lung mass is needed to prevent
unnecessary invasive procedures and surgery.
Still, the study cohorts used here are retrospective, and
a prospective validation trial is needed to understand the full clinical
potential of the blood test. Additionally, the authors note that the test
results are not integrated with clinical risk factors, although they also note
that “pulmonologists vary broadly in the use of clinical risk factors, and so,
it is actually preferable to have a molecular diagnostic test that produces a
score independent of clinical risk factors.”
Even if validated, it is likely that such a blood test
will be part of the other information used by clinicians to make the
best-informed decision for each individual patient.
Stephen Malkoski, MD, PhD, who specializes in pulmonary
medicine at the University of Colorado Cancer Center in Aurora and who was not
involved in the research, says interpreting the test results would likely
depend on the calculated risk clinicians currently use to assess whether a
nodule could be cancerous. Factors that go into the risk calculation include
size of the nodule, its location, smoking history, age, emphysema, and family
lung cancer history. “In a low-risk patient with a 1% to 2% risk of lung
cancer, the patient would still likely need a follow-up CT scan since the blood
test could not definitely exclude malignancy.”
Malkoski sees the test as potentially being the most
helpful in intermediate-risk patients with a calculated risk of malignancy
between 10% and 20%. “In this group, a negative test might obviate the need for
additional workup, such as a PET scan or biopsy,” he notes. “This may make a
clinician more comfortable opting for radiographic follow-up rather than an
invasive procedure.”
