domingo, 9 de julio de 2017

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer. - PubMed - NCBI

2017 Jun 17. pii: S1556-0864(17)30461-6. doi: 10.1016/j.jtho.2017.06.008. [Epub ahead of print]

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer.

Barón AE1, Kako S2, Feser WJ3, Malinowski H4, Merrick D4, Garg K5, Malkoski S6, Pretzel S7, Siegfried JM8, Franklin WA4, Miller Y9, Wolf HJ10, Varella-Garcia M2.

Author information

Abstract

INTRODUCTION:

Low dose CT screening for lung cancer has a high false positive rate with frequent discovery of indeterminate pulmonary nodules. Noninvasive biomarkers are needed to reduce false positives and improve risk stratification. A retrospective longitudinal evaluation was performed to assess chromosomal aneusomy in sputum via fluorescence in situ hybridization (CA-FISH) in four nested case-control studies.

METHODS:

ROC analysis resulted in two grouped cohorts: High Risk (CO High Risk and CO Nodule; 68 Cases, 69 controls) and Screening (ACRIN/NLST and PLuSS; 97 Cases, 185 controls). The CA-FISH assay was a 4-target DNA panel encompassing EGFR and MYC genes, and the 5p15 and centromere 6 regions or the FGFR1 and PIK3CA genes. A 4-category scale: normal, probably normal, probably abnormal and abnormal was applied. Sensitivity, specificity, and positive and negative likelihood ratios (LR+, LR-) (with 95% CI) were estimated for each cohort.

RESULTS:

Sensitivity and specificity were, respectively, 0.67 (0.55, 0.78) and 0.94 (0.85, 0.98) for High Risk subjects and 0.20 (0.13, 0.30) and 0.84 (0.78, 0.89) for Screening subjects. LR+ and LR- were, respectively, 11.66 (4.44, 30.63) and 0.34 (0.24, 0.48) for High Risk; and 1.36 (0.81, 2.28) and 0.93 (0.83, 1.05) for Screening subjects.

CONCLUSION:

The high positive likelihood ratio of sputum CA-FISH indicates it could be a useful adjunct to LDCT for lung cancer in high risk settings. For screening, however, its low positive likelihood ratio limits clinical utility. Prospective assessment of CA-FISH in the incidentally-identified indeterminate nodule setting is ongoing in the Colorado Pulmonary Nodule Biomarker Trial.