{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:50:10Z","timestamp":1791625810018,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp;amp; Neck"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adenoid cystic carcinoma (ACC) is a rare malignancy with a propensity for perineural invasion and hematogenous spread. Central nervous system (CNS) involvement is uncommon, and detailed clinical and genomic data on this aspect of the disease remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a single\u2010institution retrospective cohort study of patients with biopsy\u2010confirmed ACC and CNS involvement treated at the University of Pennsylvania. Clinical features, CNS disease patterns, treatment modalities, molecular alterations, and survival outcomes were abstracted from the electronic medical record.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventeen patients were identified. CNS involvement occurred a median of 40\u2009months after initial ACC diagnosis. CNS disease included parenchymal metastases, leptomeningeal disease, and patterns suggestive of neurotropic or perineural intracranial extension. Leptomeningeal involvement was present in 6 patients. Targeted next\u2010generation sequencing demonstrated NOTCH1 alterations in 7 patients, with additional recurrent alterations in CREBBP, BAP1, FGFR2, and PI3K\u2010pathway genes. CNS\u2010directed therapy included surgery, stereotactic radiosurgery, hypofractionated radiotherapy, whole\u2010brain radiotherapy, and conventionally fractionated radiotherapy. Median progression\u2010free survival was 5.4\u2009months, and median overall survival was 9.4\u2009months after CNS involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CNS involvement in ACC was associated with poor outcomes despite multimodal therapy. NOTCH1 alterations and leptomeningeal disease were frequent in this cohort, but these findings should be interpreted as hypothesis\u2010generating given the small sample size and absence of a matched non\u2010CNS comparator cohort.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70342","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:40:56Z","timestamp":1780983656000},"page":"3193-3201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinicogenomic Features and Outcomes of Adenoid Cystic Carcinoma With Central Nervous System Metastases: A Single\u2010Institution Cohort Study"],"prefix":"10.1002","volume":"48","author":[{"given":"Omar","family":"Elghawy","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Abramson Cancer Center, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Stylli","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Abramson Cancer Center, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kurian","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Abramson Cancer Center, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Halper\u2010Stromberg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Abramson Cancer Center, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"D'Avella","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Abramson Cancer Center, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Hartner","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Abramson Cancer Center, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-7435","authenticated-orcid":false,"given":"Roger B.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Abramson Cancer Center, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00020840-200404000-00013"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2015.04.005"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(97)00153-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(95)00122-F"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.10380"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(96)00464-6"},{"issue":"10","key":"e_1_2_11_8_1","first-page":"979","article-title":"Management of Adenoid Cystic Carcinoma of the Head and Neck","volume":"48","author":"Mendenhall W. M.","year":"2012","journal-title":"Oral Oncology"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70245-X"},{"issue":"5","key":"e_1_2_11_10_1","first-page":"754","article-title":"Chemotherapy and Targeted Therapy in Adenoid Cystic Carcinoma of the Head and Neck: A Systematic Review","volume":"34","author":"Papaspyrou K.","year":"2012","journal-title":"Head & Neck"},{"issue":"4","key":"e_1_2_11_11_1","first-page":"720","article-title":"Apatinib for Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck: A Phase II, Single\u2010Arm, Prospective Study","volume":"124","author":"Li N.","year":"2021","journal-title":"British Journal of Cancer"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-1061"},{"issue":"8","key":"e_1_2_11_13_1","first-page":"91","article-title":"Management of Adenoid Cystic Carcinoma of the Head and Neck: A Contemporary Review","volume":"23","author":"Phan J.","year":"2021","journal-title":"Current Oncology Reports"},{"issue":"7","key":"e_1_2_11_14_1","first-page":"635","article-title":"Treatment Approaches to Salivary Gland Carcinomas: Current Status and Future Directions","volume":"21","author":"Caponigro F.","year":"2010","journal-title":"Anti\u2010Cancer Drugs"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.01.001"},{"key":"e_1_2_11_16_1","first-page":"55","article-title":"Central Nervous System Metastases in Adenoid Cystic Carcinoma: A Review of the Literature","volume":"30","author":"Reyes M.","year":"2017","journal-title":"Annals of Diagnostic Pathology"},{"issue":"5","key":"e_1_2_11_17_1","first-page":"1078","article-title":"Brain Metastases From Head and Neck Cancer: A Study of 95 Patients","volume":"106","author":"Maire J. 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