{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:25:16Z","timestamp":1793157916069,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Usually benign, pituitary tumors (PT) can be invasive and aggressive with a propensity to progress and\/or recur. Trouillas's clinicopathological classification attempts to predict the evolutionary risk of a PT. In this study, we assessed the prognostic value of this classification in an independent patient cohort and analyzed its impact on treatment strategies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and methods<\/jats:title>\n                  <jats:p>In this study, 607 patients operated on between 2008 and 2018 for a PT were included. Grading was established based on invasion, proliferative activity (Ki-67, mitotic index) and p53 positivity. The therapeutic management following surgery was analyzed. Progression-free survival (PFS) of the graded tumors was estimated (Kaplan\u2013Meier method and log-rank test) and a multivariate analysis was performed (Cox regression model).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Grading identified non-invasive PT without (grade 1a: 303 cases) or with proliferative activity (grade 1b: 53 cases) and invasive PT without (grade 2a: 202 cases) or with proliferative activity (grade 2b: 49 cases). The mean follow-up was 47 \u00b1 30 months (median: 38 months). Progression\/recurrence occurred in 127 cases. Grades were significant and independent predictors of PFS (P\u2009&amp;lt;\u20090.001) with a 4.8-fold higher risk of progression\/recurrence in grade 2b as compared to grade 1a. As second-line therapy, gamma knife or conventional radiotherapy controlled tumor growth in 91.6 and 100% of cases, respectively, irrespective of the grade. Proliferative tumors exposed the patient to a 9.5-fold higher risk of having \u22653 adjuvant therapeutic lines as compared to non-proliferative tumors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Grading of a PT according to Trouillas's classification predicts its risk of progression and should advocate for a personalized therapeutic approach in invasive and proliferative tumors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Significance statement<\/jats:title>\n                  <jats:p>This is the first study to assess, on a cohort of 607 well-characterized patients, the real-life therapeutic impact of the five-tiered clinicopathological classification of pituitary tumors. First, we validate that pituitary tumor grades predict the evolutionary risk of the tumor, with a significant higher risk of progression\/recurrence in invasive and\/or proliferative tumors (mean follow-up: 47 \u00b1 30 months, median: 38 months). Moreover, our study provides evidence that patients with proliferative tumors have a higher risk to be retreated after primary surgery and point toward the fact that radiotherapy can successfully control tumor growth in case of progression or recurrence. Our findings advocate for a personalized therapeutic approach in clinically aggressive pituitary tumors.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1530\/eje-22-0812","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T17:17:16Z","timestamp":1667236636000},"page":"893-904","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":38,"title":["Real-life clinical impact of a five-tiered classification of pituitary tumors"],"prefix":"10.1093","volume":"187","author":[{"given":"Nicolas","family":"Sahakian","sequence":"first","affiliation":[{"name":"Aix Marseille Univ, MMG, INSERM U1251, MARMARA Institute, APHM, H\u00f4pital de la Conception, Department of Endocrinology, CRMR HYPO , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Appay","sequence":"additional","affiliation":[{"name":"APHM, CHU Timone, Service d'Anatomie Pathologique et de Neuropathologie , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mie","family":"Resseguier","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, APHM, H\u00f4pital de la Timone, Service d'Epidemiologie et d'Economie de la Sant\u00e9, Unit\u00e9 de Recherche Clinique, Direction de la Recherche en Sant\u00e9 , Marseille, France"},{"name":"EA3279, CEReSS, Health Service Research and Quality of Life Center, Aix-Marseille University , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Graillon","sequence":"additional","affiliation":[{"name":"Aix Marseille University, MMG, INSERM U1251, MARMARA Institute, APHM, H\u00f4pital de la Timone Department of Neurosurgery, CRMR HYPO , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cilia","family":"Piazzola","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, MMG, INSERM U1251, MARMARA Institute, APHM, H\u00f4pital de la Conception, Department of Endocrinology, CRMR HYPO , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cilia","family":"Laure","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital of Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Figarella-Branger","sequence":"additional","affiliation":[{"name":"APHM, CHU Timone, Service d'Anatomie Pathologique et de Neuropathologie , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"R\u00e9gis","sequence":"additional","affiliation":[{"name":"Aix Marseille University, INS-UMR1106, Department of Functional and Stereotactic Neurosurgery, CHU Timone , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-8800","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Castinetti","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, MMG, INSERM U1251, MARMARA Institute, APHM, H\u00f4pital de la Conception, Department of Endocrinology, CRMR HYPO , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8482-6691","authenticated-orcid":false,"given":"Thierry","family":"Brue","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, MMG, INSERM U1251, MARMARA Institute, APHM, H\u00f4pital de la Conception, Department of Endocrinology, CRMR HYPO , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Dufour","sequence":"additional","affiliation":[{"name":"Aix Marseille University, MMG, INSERM U1251, MARMARA Institute, APHM, H\u00f4pital de la Timone 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