Neal I. Lindeman, Philip T. Cagle, Dara L. Aisner, Maria E. Arcila, Mary Beth Beasley, Eric Bernicker, Carol Colasacco, Sanja Dacic, Fred R. Hirsch, Keith Kerr, David J. Kwiatkowski, Marc Ladanyi, Jan A. Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benjamin Solomon, Lesley H. Souter, Erik Thunnissen, Ming S. Tsao, Christina B. Ventura, Murry W. Wynes, and Yasushi Yatabe (2018) Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Archives of Pathology & Laboratory Medicine In-Press.

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Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

Neal I. Lindeman, MD; Philip T. Cagle, MD; Dara L. Aisner, MD, PhD; Maria E. Arcila, MD; Mary Beth Beasley, MD; Eric Bernicker, MD;Carol Colasacco, MLIS, SCT(ASCP); Sanja Dacic, MD, PhD; Fred R. Hirsch, MD, PhD; Keith Kerr, MB, ChB; David J. Kwiatkowski, MD, PhD; Marc Ladanyi, MD; Jan A. Nowak, MD, PhD; Lynette Sholl, MD; Robyn Temple-Smolkin, PhD; Benjamin Solomon, MBBS, PhD; Lesley H. Souter, PhD; Erik Thunnissen, MD, PhD; Ming S. Tsao, MD; Christina B. Ventura, MPH, MT(ASCP); Murry W. Wynes, PhD; Yasushi Yatabe, MD, PhD

From the Departments of Pathology (Drs Lindeman and Sholl) and Medicine (Dr Kwiatkowski), Brigham and Women's Hospital, Boston, Massachusetts; the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Dr Cagle); the Department of Pathology, University of Colorado School of Medicine, Denver (Dr Aisner); the Diagnostic and Molecular Pathology Laboratory (Dr Arcila) and the Molecular Diagnostics Service (Dr Ladanyi), Memorial Sloan Kettering Cancer Center, New York, New York; the Department of Pathology & Medicine, Pulmonary, Critical Care and Sleep Medicine, New York, New York (Dr Beasley); the Cancer Research Program, Houston Methodist Research Institute, Houston, Texas (Dr Bernicker); the Pathology and Laboratory Quality Center, College of American Pathologists, Northfield, Illinois (Mss Colasacco and Ventura); the Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Dacic); the Department of Medicine and Pathology, University of Colorado, Denver (Dr Hirsch); the Department of Pathology, University of Aberdeen, Aberdeen, Scotland (Dr Kerr); the Department of Molecular Pathology, Roswell Park Cancer Institute, Buffalo, New York (Dr Nowak); the Clinical and Scientific Affairs Division, Association for Molecular Pathology, Bethesda, Maryland (Dr Temple-Smolkin); the Molecular Therapeutics and Biomarkers Laboratory, Peter Maccallum Cancer Center, Melbourne, Australia (Dr Solomon); the Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands (Dr Thunnissen); the Department of Laboratory Medicine and Pathobiology, Princess Margaret Cancer Center, Toronto, Ontario, Canada (Dr Tsao); Scientific Affairs, International Association for the Study of Lung Cancer, Aurora, Colorado (Dr Wynes); and the Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan (Dr Yatabe). Dr Souter is in private practice in Wellanport, Ontario, Canada.

Reprints: Neal I. Lindeman, MD, Brigham and Women's Hospital, Department of Pathology, 75 Francis St, Shapiro 5, Room 020, Boston, MA 02115 (email: nlindeman@partners.org).

Supplemental digital content is available for this article. See text for hyperlink.

Authors' disclosures of potential conflicts of interest and author contributions are found in the Appendix at the end of this article.

This guideline was developed through collaboration among the College of American Pathologists, the International Association for the Study of Lung Cancer, the Association for Molecular Pathology, and the American Society for Investigative Pathology and has been jointly published by invitation and consent in the Archives of Pathology & Laboratory Medicine, Journal of Thoracic Oncology, and The Journal of Molecular Diagnostics. Copyright 2018 College of American Pathologists, International Association for the Study of Lung Cancer, Association for Molecular Pathology, and American Society for Investigative Pathology.

Context.— In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing.

Objective.— To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update.

Design.— The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations.

Results.— Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline.

Conclusions.— The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes (ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to “rule in” targetable mutations when tissue is limited or hard to obtain.

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