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    Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation

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    Authors
    Feeney, Laura
    Hapuarachi, Brindley
    Adderley, Helen
    Rack, Samuel
    Morgan, D.
    Walker, R.
    Rauch, R.
    Herz, E.
    Kaye, J.
    Harrington, K.
    Metcalf, Robert
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    Affiliation
    The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK
    Issue Date
    2022
    
    Metadata
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    Abstract
    Background: Adenoid cystic carcinoma (ACC) is a rare salivary cancer. The highest rates of disease recurrence are in patients with NOTCH pathway activation, reported in up to 20%. Novel drugs targeting NOTCH signaling are under investigation in the recurrent/metastatic (R/M) setting. To understand their clinical utility, there is an urgent need to better characterize the disease course and outcomes following current standard of care treatment. Methods: 120 patients with R/M ACC underwent clinical review at a single UK Cancer Centre. Patients were retrospectively assessed for tumor NOTCH pathway activation using next generation sequencing (NGS) targeting NOTCH1/2/3 genes and/or NOTCH1 intra-cellular domain (NICD1) immunohistochemistry. Demographic and treatment data were extracted from the clinical notes. Kaplan-Meier survival analysis was performed using log rank test. Results: NOTCH pathway activation was identified in 13/120 patients (11 %). In 12/101 patients analyzed by NGS, NOTCH1/3 activating somatic mutations were identified, and a further patient was identified with NICD1 diffuse nuclear staining in whom NGS testing was not possible. Patients with NOTCH pathway activation had shorter median RFS (1.1 vs 3.4 years, p = 0.2032) and significantly reduced median OS from diagnosis (4.0 vs 16.3 years, p < 0.0001). There was significantly reduced median OS from time of disease recurrence/metastasis (1.9 vs 9.6 years, p < 0.0001). Conclusion: This study clearly demonstrates a reduction in OS from time of first confirmed disease recurrence/metastasis for patients with NOTCH pathway activated ACC. This provides support for developing new drugs for this sub-group of patients, for whom clinical outcomes are significantly worse and effective treatments are lacking.
    Citation
    Feeney L, Hapuarachi B, Adderley H, Rack S, Morgan D, Walker R, et al. Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation. Oral oncology. 2022 Aug 8;133:106028. PubMed PMID: 35952580. Epub 2022/08/12. eng.
    Journal
    Oral Oncology
    URI
    http://hdl.handle.net/10541/625561
    DOI
    10.1016/j.oraloncology.2022.106028
    PubMed ID
    35952580
    Additional Links
    https://dx.doi.org/10.1016/j.oraloncology.2022.106028
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.oraloncology.2022.106028
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