http://www.archivesofpathology.org/doi/abs/10.5858/arpa.2012-0720-OA

Neal I. Lindeman, Philip T. Cagle, Mary Beth Beasley, Dhananjay Arun Chitale, Sanja Dacic, Giuseppe Giaccone, Robert Brian Jenkins, David J. Kwiatkowski, Juan-Sebastian Saldivar, Jeremy Squire, Erik Thunnissen, and Marc Ladanyi (2013) Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology

Neal I. Lindeman , MD; Philip T. Cagle , MD; Mary Beth Beasley , MD; Dhananjay Arun Chitale , MD; Sanja Dacic , MD, PhD;Giuseppe Giaccone , MD, PhD; Robert Brian Jenkins , MD, PhD; David J. Kwiatkowski , MD, PhD; Juan-Sebastian Saldivar , MD;Jeremy Squire , PhD; Erik Thunnissen , MD, PhD; Marc Ladanyi , MD

From the Departments of Pathology (Dr Lindeman) and Medicine (Dr Kwiatkowski), Brigham & Women's Hospital, Boston, Massachusetts; the Department of Pathology and Genomic Medicine, The Methodist Hospital, Houston, Texas (Dr Cagle); the Department of Pathology, Mt Sinai Medical Center, New York, New York (Dr Beasley); the Department of Pathology, Henry Ford Hospital, Detroit, Michigan (Dr Chitale); the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dr Dacic); the Medical Oncology Branch, National Institutes of Health, Bethesda, Maryland (Dr Giaccone); the Department of Laboratory Medicine and Pathology, Department of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota (Dr Jenkins); the Department of Pathology, City of Hope National Medical Center, Duarte, California (Dr Saldivar); the Department of Pathology and Molecular Medicine, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada (Dr Squire); the Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands (Dr Thunnissen); and the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (Dr Ladanyi).

Objective.—To establish evidence-based recommendations for the molecular analysis of lung cancers that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed.

Participants.—Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies.

Evidence.—Three unbiased literature searches of electronic databases were performed to capture articles published from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation.

Consensus Process.—Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4).

Conclusions.—The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritizeEGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines.