dc.contributor.author | Feeney, L | |
dc.contributor.author | Hapuarachi, B | |
dc.contributor.author | Adderley, H | |
dc.contributor.author | Rack, S | |
dc.contributor.author | Morgan, D | |
dc.contributor.author | Walker, R | |
dc.contributor.author | Rauch, R | |
dc.contributor.author | Herz, E | |
dc.contributor.author | Kaye, J | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Metcalf, R | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-10-18T09:38:56Z | |
dc.date.available | 2022-10-18T09:38:56Z | |
dc.date.issued | 2022-10-01 | |
dc.identifier | 106028 | |
dc.identifier | S1368-8375(22)00317-7 | |
dc.identifier.citation | Oral Oncology, 2022, 133 pp. 106028 - | |
dc.identifier.issn | 1368-8375 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5544 | |
dc.identifier.eissn | 1879-0593 | |
dc.identifier.eissn | 1879-0593 | |
dc.identifier.doi | 10.1016/j.oraloncology.2022.106028 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 106028 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | Oral Oncology | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Adenoid cystic carcinoma | |
dc.subject | NOTCH pathway activation | |
dc.subject | Salivary gland cancer | |
dc.subject | Carcinoma, Adenoid Cystic | |
dc.subject | Humans | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Retrospective Studies | |
dc.subject | Salivary Gland Neoplasms | |
dc.subject | Signal Transduction | |
dc.title | Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-07-15 | |
dc.date.updated | 2022-10-18T09:38:24Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.oraloncology.2022.106028 | |
rioxxterms.licenseref.startdate | 2022-10-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35952580 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.oraloncology.2022.106028 | |
pubs.volume | 133 | |
icr.researchteam | Targeted Therapy | |
dc.contributor.icrauthor | Harrington, Kevin | |
icr.provenance | Deposited by Mr Arek Surman on 2022-10-18. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S1368837522003177-main.pdf | |