{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:01:27Z","timestamp":1773921687225,"version":"3.50.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"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>Background<\/jats:title><jats:p>To evaluate the efficacy and safety of everolimus, a mTOR inhibitor, on invasive malignant renal epithelioid angiomyolipoma (EAML).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>From Oct 2014 to May 2019, we collected data from seven patients with a definite (clinical and pathological) diagnosis of EAML received everolimus in our hospital. Targeted sequence capture array technique with next-generation of high throughput sequencing (NGS) were performed to detect mutations of TSC1\/2 genes. All patients had received surgery and everolimus. The clinical efficacy and safety of the therapy were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mutations of TSC1 and TSC2 were detected in two and three patients though targeted sequence capture array technique with NGS, respectively. Among seven patients, three had missense mutations, one had nonsense mutation, and one had the large fragment deletion mutation. Five patients accompanied with tuberous sclerosis complex (TSC) were identified. All patients were administered 10mg everolimus once daily, the treatment duration lasted for 3 to 28 months. The objective response was assessed 3 months later, five partial response, two stable disease (SD), the mean greatest tumor diameter of all patients decreased from 9.6 to 5.2cm. Six patients stayed SD and one patient died during follow up. Patients accompanying with TSC had better responses to everolimus compared with non-TSC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The mTOR inhibitor can be an effective treatment for patients with invasive malignant renal EAML. Patients with TSC may benefit more from the therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2020.610858","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T08:21:58Z","timestamp":1611649318000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Everolimus in Invasive Malignant Renal Epithelioid Angiomyolipoma"],"prefix":"10.3389","volume":"10","author":[{"given":"Gang","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangyou","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.eururo.2016.01.048","article-title":"Natural History of Renal Angiomyolipoma (AML): Most Patients with Large AMLs >4cm Can Be Offered Active Surveillance as an Initial Management Strategy","volume":"70","author":"Bhatt","year":"2016","journal-title":"Eur Urol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00838.x","article-title":"Renal angiomyolipomata","volume":"66","author":"Bissler","year":"2004","journal-title":"Kidney Int"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.72","article-title":"Epithelioid angiomyolipoma of the kidney: pathological features and clinical outcome in a series of consecutively resected tumors","volume":"26","author":"He","year":"2013","journal-title":"Mod Pathol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31817ed7a6","article-title":"Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association","volume":"33","author":"Aydin","year":"2009","journal-title":"Am J Surg Pathol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00261-012-9903-5","article-title":"Beyond renal cell carcinoma: rare and unusual renal masses","volume":"37","author":"Raman","year":"2012","journal-title":"Abdom Imaging"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19981015)83:8<1581::AID-CNCR13>3.0.CO;2-R","article-title":"Atypical angiomyolipoma of the kidney: a distinct morphologic variant that is easily confused with a variety of malignant neoplasms","volume":"83","author":"Delgado","year":"1998","journal-title":"Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.01.028","article-title":"Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms","volume":"38","author":"Kenerson","year":"2007","journal-title":"Hum Pathol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"B9","unstructured":"Common Terminology Criteria for Adverse Events, Version 4.0, DCTD, NCI, NIH, DHHS May 28, 20092009"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.20459","article-title":"Rapid estimation of whole blood everolimus concentrations using architect sirolimus immunoassay and mathematical equations: comparison with everolimus values determined by liquid chromatography\/mass spectrometry","volume":"25","author":"Dasgupta","year":"2011","journal-title":"J Clin Lab Anal"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22522","article-title":"Expanding the mutational spectrum of CRLF1 in Crisponi\/CISS1 syndrome","volume":"35","author":"Piras","year":"2014","journal-title":"Hum Mutat"},{"key":"B12","doi-asserted-by":"publisher","first-page":"10030","DOI":"10.1038\/srep10030","article-title":"A Four-Year Follow-up Study of Renal Epithelioid Angiomyolipoma: A Multi-Center Experience and Literature Review","volume":"5","author":"Lei","year":"2015","journal-title":"Sci Rep"},{"key":"B13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.5301\/JN.2010.5451","article-title":"Renal epithelioid angiomyolipoma: a malignant disease","volume":"24","author":"Varma","year":"2011","journal-title":"J Nephrol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3840","article-title":"Estrogen enhances whereas tamoxifen retards development of Tsc mouse liver hemangioma: a tumor related to renal angiomyolipoma and pulmonary lymphangioleiomyomatosis","volume":"65","author":"El-Hashemite","year":"2005","journal-title":"Cancer Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S1607-551X(09)70052-X","article-title":"Epithelioid angiomyolipoma of the kidney mimicking renal cell carcinoma: a clinicopathologic analysis of cases and literature review","volume":"25","author":"Tsai","year":"2009","journal-title":"Kaohsiung J Med Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.12.8776","article-title":"Renal epithelioid angiomyolipoma: imaging characteristics in nine cases with radiologic-pathologic correlation and review of the literature","volume":"200","author":"Froemming","year":"2013","journal-title":"AJR Am J Roentgenol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S61524","article-title":"Comprehensive clinical and pathological analysis of aggressive renal epithelioid angiomyolipoma: report of three cases","volume":"7","author":"Luo","year":"2014","journal-title":"Onco Targets Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyr035","article-title":"Dramatic tumor response to everolimus for malignant epithelioid angiomyolipoma","volume":"41","author":"Shitara","year":"2011","journal-title":"Jpn J Clin Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2006.01665.x","article-title":"Clinical presentation of epithelioid angiomyolipoma","volume":"14","author":"Park","year":"2007","journal-title":"Int J Urol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200101000-00014","article-title":"Malignant epithelioid angiomyolipoma (\u2018sarcoma ex angiomyolipoma\u2019) of the kidney: a case report and review of the literature","volume":"25","author":"Cibas","year":"2001","journal-title":"Am J Surg Pathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61767-X","article-title":"Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial","volume":"381","author":"Bissler","year":"2013","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1186\/s12885-018-4467-6","article-title":"Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation","volume":"18","author":"Espinosa","year":"2018","journal-title":"BMC Cancer"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-017-1629-4","article-title":"Clinical presentations and molecular studies of invasive renal epithelioid angiomyolipoma","volume":"49","author":"Chuang","year":"2017","journal-title":"Int Urol Nephrol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.5489\/cuaj.2823","article-title":"Malignant epitheloid angiomyolipoma of the kidney in a child treated with sunitinib, everolimus and axitinib","volume":"9","author":"Citak","year":"2015","journal-title":"Can Urol Assoc J"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.610858\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T08:22:06Z","timestamp":1611649326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.610858\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,26]]},"references-count":24,"alternative-id":["10.3389\/fonc.2020.610858"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2020.610858","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,26]]},"article-number":"610858"}}