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Depending on the clinical course of the disease, interdisciplinary treatment concepts are required, including surgery, radiotherapy and systemic cancer therapy. However, due to its uncommonness, standard treatment options are lacking so far, especially in advanced disease with distant metastases.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods and results<\/jats:title>\n                <jats:p>Here we report on an unusual case of a patient with metastasized EHE showing long-term response to second line treatment with gemcitabine over almost 2 decades. Cancer genome sequencing of the patient\u2019s tumor tissue detected a NOTCH3 missense mutation which could provide an explanation for these clinical findings. NOTCH3 is known to be a mediator of resistance towards gemcitabine-based cancer treatment, at least in pancreatic cancer and non-small cell lung cancer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The observation that this missense mutation of NOTCH3 is associated with an increased response to treatment with gemcitabine in EHE can be used prospectively to assess NOTCH3 as potential biomarker for predicting therapy response to gemcitabine.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-023-04598-1","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T11:23:08Z","timestamp":1675768988000},"page":"6753-6757","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NOTCH3 missense mutations as predictor of long-term response to gemcitabine in a patient with epithelioid hemangioendothelioma"],"prefix":"10.1007","volume":"149","author":[{"given":"Moritz","family":"Schmidt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Mattern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Singer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia","family":"Biskup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Krumm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich M.","family":"Lauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Zender","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens","family":"Hinterleitner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Hinterleitner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"issue":"6","key":"4598_CR1","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1111\/j.1440-1843.2006.00923.x","volume":"11","author":"RM Amin","year":"2006","unstructured":"Amin RM, Hiroshima K, Kokubo T, Nishikawa M, Narita M, Kuroki M, Nakatani Y (2006) Risk factors and independent predictors of survival in patients with pulmonary epithelioid haemangioendothelioma. 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