Improving Selection Criteria for ALK Inhibitor Therapy in Non-Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry

The American Journal of Surgical Pathology
Long JiangJianxing He

Abstract

Lung cancer is often diagnosed by molecular markers for prediction and treatment. To date, the golden standard for detection of anaplastic lymphoma kinase (ALK) rearrangements is fluorescence in situ hybridization (FISH). We performed a pooled-data analysis on the diagnostic operating characteristics of immunohistochemistry (IHC) assay on non-small cell lung cancer (NSCLC). We searched Embase, Pubmed, and Springer databases. The results of IHC were evaluated using a modified H-score. We used a 2-level bivariate meta-analysis following a random effect model to summarize sensitivity and specificity and fit hierarchical summary receiver-operating characteristic curves. We also performed sensitivity analysis using different antibodies to investigate potential heterogeneity. Twelve studies consisting of a total of 3754 NSCLC specimens were analyzed. When we defined 1+/2+/3+, 2+/3+, and 3+ as ALK positive, we found the sensitivities to be 99% (95% confidence interval [CI], 97%-100%), 86% (95% CI, 73%-93%), and 56% (95% CI, 36%-74%) and the specificities to be 98% (95% CI, 95%-99%), 99% (95% CI, 99%-100%), and 100% (95% CI, 100%-100%), respectively. We demonstrated that when defining 3+ as positive and 0 as negative the sensitivity wa...Continue Reading

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Citations

Dec 24, 2016·Cancer Biomarkers : Section a of Disease Markers·Anna CaliòMatteo Brunelli
Aug 31, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K M Kerr, F López-Ríos
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Aug 28, 2020·Frontiers in Cell and Developmental Biology·Wenjian ChenJun Sun
Oct 5, 2020·The Journal of Molecular Diagnostics : JMD·Cleo KeppensElisabeth M C Dequeker
Jul 24, 2021·Breathe·Marie DrosslerovaLibor Havel

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Methods Mentioned

BETA
surgical
biopsies

Software Mentioned

Quality Assessment of Diagnostic Accuracy Studies - 2 ( QUADAS...

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