Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation
AffiliationThe Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK
MetadataShow full item record
AbstractBackground: 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.
CitationFeeney 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.
- Diffuse Staining for Activated NOTCH1 Correlates With NOTCH1 Mutation Status and Is Associated With Worse Outcome in Adenoid Cystic Carcinoma.
- Authors: Sajed DP, Faquin WC, Carey C, Severson EA, H Afrogheh A, A Johnson C, Blacklow SC, Chau NG, Lin DT, Krane JF, Jo VY, Garcia JJ, Sholl LM, Aster JC
- Issue date: 2017 Nov
- Alterations of Notch pathway in patients with adenoid cystic carcinoma of the trachea and its impact on survival.
- Authors: Xie M, Wei S, Wu X, Li X, You Y, He C
- Issue date: 2018 Jul
- AL101, a gamma-secretase inhibitor, has potent antitumor activity against adenoid cystic carcinoma with activated NOTCH signaling.
- Authors: Ferrarotto R, Mishra V, Herz E, Yaacov A, Solomon O, Rauch R, Mondshine A, Motin M, Leibovich-Rivkin T, Davis M, Kaye J, Weber CR, Shen L, Pearson AT, Rosenberg AJ, Chen X, Singh A, Aster JC, Agrawal N, Izumchenko E
- Issue date: 2022 Aug 5
- Notch-4 contributes to the metastasis of salivary adenoid cystic carcinoma.
- Authors: Ding LC, She L, Zheng DL, Huang QL, Wang JF, Zheng FF, Lu YG
- Issue date: 2010 Aug
- Activating NOTCH1 Mutations Define a Distinct Subgroup of Patients With Adenoid Cystic Carcinoma Who Have Poor Prognosis, Propensity to Bone and Liver Metastasis, and Potential Responsiveness to Notch1 Inhibitors.
- Authors: Ferrarotto R, Mitani Y, Diao L, Guijarro I, Wang J, Zweidler-McKay P, Bell D, William WN Jr, Glisson BS, Wick MJ, Kapoun AM, Patnaik A, Eckhardt G, Munster P, Faoro L, Dupont J, Lee JJ, Futreal A, El-Naggar AK, Heymach JV
- Issue date: 2017 Jan 20