{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T16:18:08Z","timestamp":1782663488415,"version":"3.54.5"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Expression of the <jats:italic>NTRK<\/jats:italic> gene is rare in solid tumors but is highly prevalent in salivary gland secretory carcinomas. Here, we report a case of a complete response to entrectinib in a patient with <jats:italic>NTRK<\/jats:italic> fusion gene-positive parotid carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case description<\/jats:title><jats:p>The patient was a 44-year-old man who underwent total left parotidectomy and left cervical lymph node dissection for a left parotid tumor at 24 years of age. The histopathological diagnosis was mammary analog secretory carcinoma. Postoperatively, the patient received only radiation therapy. Sixteen years after the surgery, the patient became aware of a mass in the left parotid region. A close examination revealed local recurrence and multiple cervical lymph node metastases. S-1 monotherapy was started as chemotherapy but was discontinued 3 years later because of disease progression. As there was no standard treatment, a comprehensive genomic profiling test using a next-generation sequencer was performed, and the <jats:italic>ETV6-NTRK3<\/jats:italic> fusion gene was identified. Entrectinib, an <jats:italic>NTRK<\/jats:italic> inhibitor, was immediately administered at a dose of 600 mg\/day. The local recurrence rapidly shrank grossly from the beginning of treatment, and a complete response was observed 6 months later. However, creatinine levels exhibited an increase at week 68 of treatment; consequently, entrectinib dosage was lowered to 400 mg\/day, leading to an immediate improvement in creatinine levels. Entrectinib was associated with additional side effects, including dysgeusia, fatigue, dizziness, and weight gain, all of which were also alleviated by the reduction in entrectinib dose. Thirty months after treatment initiation, the patient maintained a complete response and continued to receive entrectinib.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>NTRK<\/jats:italic> fusion gene should always be checked in the presence of salivary gland secretory carcinoma.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1247435","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:16:27Z","timestamp":1691151387000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Case Report: A case of complete response to entrectinib in NTRK fusion gene-positive parotid gland cancer"],"prefix":"10.3389","volume":"13","author":[{"given":"Etsuko","family":"Moriyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Nagasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimitsu","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Shimotsuura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeharu","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohito","family":"Umeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Akiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Kawahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Miwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1097\/PAS.0b013e3181d9efcc","article-title":"Mammary analogue secretory carcinoma of salivary glands, containing the etv6-ntrk3 fusion gene: A hitherto undescribed salivary gland tumor entity","volume":"34","author":"Skalova","year":"2010","journal-title":"Am J Surg Pathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnci.2017.03.003","article-title":"Editor's perspective on the 4th edition of the who head and neck tumor classification","volume":"29","author":"El-Naggar","year":"2017","journal-title":"J Egypt Natl Canc Inst"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2012.04232.x","article-title":"Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands","volume":"61","author":"Chiosea","year":"2012","journal-title":"Histopathology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182841554","article-title":"Most nonparotid \"Acinic cell carcinomas\" Represent mammary analog secretory carcinomas","volume":"37","author":"Bishop","year":"2013","journal-title":"Am J Surg Pathol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30691-6","article-title":"Entrectinib in patients with advanced or metastatic ntrk fusion-positive solid tumours: integrated analysis of three phase 1-2 trials","volume":"21","author":"Doebele","year":"2020","journal-title":"Lancet Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000392","article-title":"Mammary analogue secretory carcinoma of salivary glands: A clinicopathologic and molecular study including 2 cases harboring etv6-X fusion","volume":"39","author":"Ito","year":"2015","journal-title":"Am J Surg Pathol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/PAS.0000000000000537","article-title":"Mammary analogue secretory carcinoma of salivary glands: molecular analysis of 25 etv6 gene rearranged tumors with lack of detection of classical etv6-ntrk3 fusion transcript by standard rt-pcr: report of 4 cases harboring etv6-X gene fusion","volume":"40","author":"Skalova","year":"2016","journal-title":"Am J Surg Pathol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21594","article-title":"Diagnostic utility of phosphorylated signal transducer and activator of transcription 5 immunostaining in the diagnosis of mammary analogue secretory carcinoma of the salivary gland: A comparative study of salivary gland cancers","volume":"123","author":"Kawahara","year":"2015","journal-title":"Cancer Cytopathol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24254","article-title":"Mammary analogue secretory carcinoma: update on a new diagnosis of salivary gland Malignancy","volume":"124","author":"Sethi","year":"2014","journal-title":"Laryngoscope"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-014-1701-8","article-title":"Mammary analogue secretory carcinoma of salivary glands: A new entity associated with etv6 gene rearrangement","volume":"466","author":"Majewska","year":"2015","journal-title":"Virchows Arch"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318242a5b0","article-title":"The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma","volume":"36","author":"Chiosea","year":"2012","journal-title":"Am J Surg Pathol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/PO.18.00183","article-title":"Analysis of ntrk alterations in pan-cancer adult and pediatric Malignancies: implications for ntrk-targeted therapeutics","volume":"2018","author":"Okamura","year":"2018","journal-title":"JCO Precis Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-0090","article-title":"Tumor-agnostic precision medicine from the aacr genie database: clinical implications","volume":"29","author":"Gouda","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.03.017","article-title":"Utility of mammaglobin immunohistochemistry as a proxy marker for the etv6-ntrk3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma","volume":"44","author":"Bishop","year":"2013","journal-title":"Hum Pathol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-3096","article-title":"Etv6-ntrk3-mediated breast epithelial cell transformation is blocked by targeting the igf1r signaling pathway","volume":"71","author":"Tognon","year":"2011","journal-title":"Cancer Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.bbrc.2012.10.087","article-title":"Etv6-ntrk3 as a therapeutic target of small molecule inhibitor pkc412","volume":"429","author":"Chi","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw042","article-title":"What hides behind the masc: clinical response and acquired resistance to entrectinib after etv6-ntrk3 identification in a mammary analogue secretory carcinoma (Masc)","volume":"27","author":"Drilon","year":"2016","journal-title":"Ann Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-1237","article-title":"Safety and antitumor activity of the multitargeted pan-trk, ros1, and alk inhibitor entrectinib: combined results from two phase I trials (Alka-372-001 and startrk-1)","volume":"7","author":"Drilon","year":"2017","journal-title":"Cancer Discov"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30856-3","article-title":"Larotrectinib in patients with trk fusion-positive solid tumours: A pooled analysis of three phase 1\/2 clinical trials","volume":"21","author":"Hong","year":"2020","journal-title":"Lancet Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol29060314","article-title":"Trk inhibition with entrectinib in metastatic salivary secretory carcinoma (Sc): A case report","volume":"29","author":"Ernst","year":"2022","journal-title":"Curr Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1247435\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:16:35Z","timestamp":1691151395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1247435\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":20,"alternative-id":["10.3389\/fonc.2023.1247435"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2023.1247435","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]},"article-number":"1247435"}}