{
    "abstract": "Effective treatments for patients with advanced lung carcinoids remain limited. The prevalence of potentially actionable genomic alterations (AGAs) among lung carcinoids is not well-understood.\nLung carcinoids submitted for next-generation sequencing (NGS) at a Clinical Laboratory Improvement Amendments (CLIA)-certified genomics laboratory from September 2013 to March 2024 were retrospectively investigated to determine prevalence of AGAs. We evaluated outcomes with genotype-matched targeted therapies in patients with advanced lung carcinoids with AGAs identified across 3 institutions and comprehensive literature search.\nAmong 321 cases of lung carcinoids profiled by NGS, 8 (2.5%) harbored potential AGAs (4 [1.2%] with commercially available targeted therapies), including KRAS mutations (n = 4, 1.2%: G12C, G12D, G12R, G12V), ALK fusions (n = 2, 0.6%), BRAF D594N (n = 1, 0.3%), and RET fusion (n = 1, 0.3%). None of the 24 typical carcinoids harbored an AGA. Collectively across these database-identified patients, our multi-institutional cohort, and literature review, we identified 36 cases of lung carcinoids with potential AGAs (24 with commercially available targeted therapies), predominantly comprising fusions of ALK (n = 14), RET (n = 5), and NTRK (n = 2). Of 27 with known disease stage, 19 had stage 4 disease, and 13 (68.4%) had outcomes reported following targeted therapies. Median treatment duration was 12.0 months (95% CI: 6.7-16.0). Median progression-free survival (PFS) was 10.6 months (95% CI: 6.7-16.0) across all targeted therapy lines and 14.0 months (95% CI: 1.3-NA) with first-line targeted therapies. Objective response rate with at least one targeted therapy was 61.5%.\nPatients with advanced lung carcinoids harboring AGAs can derive meaningful benefit from genotype-matched targeted therapies, highlighting potential role for NGS in patients with advanced carcinoids.",
    "authors": [
        {
            "affiliation": "Massachusetts General Hospital Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, MA.",
            "firstname": "Sarah",
            "initials": "S",
            "lastname": "Waliany"
        },
        {
            "affiliation": "Department of Pathology, Massachusetts General Hospital, Boston, MA.",
            "firstname": "Yin P",
            "initials": "YP",
            "lastname": "Hung"
        },
        {
            "affiliation": "Henry Ford Cancer Institute/Henry Ford Health, Detroit, MI.",
            "firstname": "Fawzi Abu",
            "initials": "FA",
            "lastname": "Rous"
        },
        {
            "affiliation": "Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA.",
            "firstname": "Faustine",
            "initials": "F",
            "lastname": "Luo"
        },
        {
            "affiliation": "Caris Life Sciences, Irving, TX.",
            "firstname": "Marzia",
            "initials": "M",
            "lastname": "Capelletti"
        },
        {
            "affiliation": "Caris Life Sciences, Irving, TX.",
            "firstname": "Steven",
            "initials": "S",
            "lastname": "Ressler"
        },
        {
            "affiliation": "Massachusetts General Hospital Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, MA.",
            "firstname": "Andrew",
            "initials": "A",
            "lastname": "Do"
        },
        {
            "affiliation": "Massachusetts General Hospital Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, MA.",
            "firstname": "Jennifer",
            "initials": "J",
            "lastname": "Peterson"
        },
        {
            "affiliation": "Henry Ford Cancer Institute/Henry Ford Health, Detroit, MI.",
            "firstname": "Caitlin",
            "initials": "C",
            "lastname": "Meservey"
        },
        {
            "affiliation": "Department of Radiology, Massachusetts General Hospital, Boston, MA.",
            "firstname": "Subba R",
            "initials": "SR",
            "lastname": "Digumarthy"
        },
        {
            "affiliation": "Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA.",
            "firstname": "Sai-Hong Ignatius",
            "initials": "SI",
            "lastname": "Ou"
        },
        {
            "affiliation": "Henry Ford Cancer Institute/Henry Ford Health, Detroit, MI.",
            "firstname": "Shirish M",
            "initials": "SM",
            "lastname": "Gadgeel"
        },
        {
            "affiliation": "Massachusetts General Hospital Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, MA. Electronic address: jjlin1@mgb.org.",
            "firstname": "Jessica J",
            "initials": "JJ",
            "lastname": "Lin"
        },
        {
            "affiliation": "Massachusetts General Hospital Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, MA. Electronic address: cbmeador@mgh.harvard.edu.",
            "firstname": "Catherine B",
            "initials": "CB",
            "lastname": "Meador"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025. Published by Elsevier Inc.",
    "doi": "10.1016/j.cllc.2025.03.009",
    "journal": "Clinical lung cancer",
    "keywords": [
        "Advanced lung carcinoids",
        "Fusion drivers",
        "Genotype-matched therapies",
        "Next-generation sequencing",
        "Targetable alterations"
    ],
    "methods": null,
    "publication_date": "2025-04-16",
    "pubmed_id": "40234130",
    "results": "Among 321 cases of lung carcinoids profiled by NGS, 8 (2.5%) harbored potential AGAs (4 [1.2%] with commercially available targeted therapies), including KRAS mutations (n = 4, 1.2%: G12C, G12D, G12R, G12V), ALK fusions (n = 2, 0.6%), BRAF D594N (n = 1, 0.3%), and RET fusion (n = 1, 0.3%). None of the 24 typical carcinoids harbored an AGA. Collectively across these database-identified patients, our multi-institutional cohort, and literature review, we identified 36 cases of lung carcinoids with potential AGAs (24 with commercially available targeted therapies), predominantly comprising fusions of ALK (n = 14), RET (n = 5), and NTRK (n = 2). Of 27 with known disease stage, 19 had stage 4 disease, and 13 (68.4%) had outcomes reported following targeted therapies. Median treatment duration was 12.0 months (95% CI: 6.7-16.0). Median progression-free survival (PFS) was 10.6 months (95% CI: 6.7-16.0) across all targeted therapy lines and 14.0 months (95% CI: 1.3-NA) with first-line targeted therapies. Objective response rate with at least one targeted therapy was 61.5%.",
    "title": "Lung Carcinoid Tumors With Potentially Actionable Genomic Alterations and Responses to Targeted Therapies.",
    "xml": "<Element 'PubmedArticle' at 0x788505afd670>"
}