{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:54:16Z","timestamp":1791251656100,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["J Neuroendocrinology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Everolimus 10\u2009mg daily is the standard dose for advanced neuroendocrine tumors (NETs), but adverse events frequently necessitate dose reduction. As a result, oncologists often adopt a dose\u2010escalation strategy starting at 5\u2009mg and increasing the dose as tolerated. In this multicenter study, we evaluated the effect of reduced dose (RD) and standard dose (SD) everolimus on survival, progression, and toxicity in patients with advanced NETs. We conducted a multicenter retrospective cohort study of patients with advanced NETs treated with everolimus at Mayo Clinic and University Hospitals (Cleveland, OH). Patients were grouped by starting dose (5\u2009mg vs. 10\u2009mg). Primary endpoints were overall survival (OS), real\u2010world progression\u2010free survival (rwPFS), and adverse events. Multivariable Cox models, inverse probability of treatment weighting (IPTW), and time\u2010varying dose sensitivity analysis were used to account for confounding and dose crossover. Among 170 patients (48 started on 5\u2009mg; 122 on 10\u2009mg), the 5\u2009mg cohort was older, had worse ECOG PS, and was more heavily pretreated. Median OS was 43.7\u2009months (5\u2009mg) versus 81.5\u2009months (10\u2009mg; log\u2010rank\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.02). However, after multivariable adjustment (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009124\u2009G1\u2013G2 patients; 51 events), the association was no longer statistically significant (adjusted HR, 0.59; 95% CI, 0.31\u20131.12;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.11). Median rwPFS was 7.0 versus 12.4\u2009months (log\u2010rank\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.05); the adjusted rwPFS difference was not statistically significant (HR, 0.95; 95% CI, 0.56\u20131.61;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.84). Nearly half (46.7%) of 10\u2009mg starters required dose reduction. Any\u2010grade toxicity was more common with 10\u2009mg (89% vs. 75%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.05). The apparent survival advantage of standard\u2010dose everolimus was substantially attenuated after adjustment. These findings do not establish dose equivalence and should be interpreted in the context of limited statistical power. Given its more favorable observed tolerability profile, RD everolimus warrants prospective evaluation as a starting strategy for patients at increased risk of treatment\u2010related toxicity who may not tolerate SD.\n                  <\/jats:p>","DOI":"10.1111\/jne.70278","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:10:26Z","timestamp":1791241826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The efficacy of standard\u2010dose versus reduced\u2010dose everolimus in patients with advanced neuroendocrine tumors: A multicenter retrospective cohort study"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9837-0891","authenticated-orcid":false,"given":"Oudai","family":"Sahwan","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6962-3535","authenticated-orcid":false,"given":"Amr","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, University Hospitals, Seidman Cancer Center Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6286-3855","authenticated-orcid":false,"given":"Fares","family":"Jamal","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5204-8102","authenticated-orcid":false,"given":"Abdullah","family":"Alsulaiman","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennah J.","family":"Bauernfeind","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Myers","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, University Hospitals, Seidman Cancer Center Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0664-9447","authenticated-orcid":false,"given":"Patrick","family":"McGarrah","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Hobday","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-8102","authenticated-orcid":false,"given":"Jason","family":"Starr","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8460-1257","authenticated-orcid":false,"given":"Thorvardur","family":"Halfdanarson","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-242X","authenticated-orcid":false,"given":"Mohamad Bassam","family":"Sonbol","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13975"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.03.304"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24983"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000457956"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0589"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30401-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00817-X"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.68.0702"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16223773"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.0988"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.5482"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jne.13319"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3050-6"}],"container-title":["Journal 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