{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:18:38Z","timestamp":1788866318462,"version":"build-2803163510"},"reference-count":24,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      The International Medullary Thyroid Carcinoma Grading System (IMTCGS) is a two-tier score that classifies high-grade medullary thyroid carcinoma (MTC) by the presence of at least one of the following features: mitotic index \u22655\/2 mm\n                      <jats:sup>2<\/jats:sup>\n                      , Ki-67 proliferation index \u22655%, or tumor necrosis. Cases lacking all three features are classified as low-grade. This study aimed to validate the prognostic role of the IMTCGS in patients with metastatic MTC. The prognostic significance of a high proliferative index (Ki-67 index \u226520%) was also investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We conducted a monocentric retrospective study of 99 metastatic MTC patients treated at Gustave Roussy between 2000 and 2024, in whom the IMTCGS was assessed on the primary tumor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      IMTCGS high-grade tumors were found in 67 patients (67.7%), who were older (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.009) and had larger primary tumors (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.001) compared with 32 patients with low-grade tumors. Postoperative calcitonin levels, number of metastatic sites\/patient, prevalence of synchronous metastases, and\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -M918T mutation were similar between groups. Median overall survival (OS) was shorter in patients with IMTCGS high-grade than low-grade (4.8 vs. 13.9 years;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.01), as was time to systemic treatment initiation (TTI) (1.0 vs. 4.8 years;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.001). However, among the 75 patients who received systemic therapy, OS from treatment initiation was similar between the two groups (2.8 vs. 3.89 years;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.865).\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -M918T mutation was not associated with worse OS. On multivariable analysis, IMTCGS high-grade and bone metastases were independently associated with both shorter OS and TTI (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.05 for both). Patients with Ki-67 index \u226520% had worse OS (2.6 years) compared with those with Ki-67 index &lt;5% (10.5 years; hazard ratio [HR] = 6.11;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.001) and 5\u201319% (6.5 years; HR = 3.29;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The IMTCGS is a strong independent prognostic factor in patients with metastatic MTC. Patients with IMTCGS high-grade tumors and Ki-67 index \u226520% represent a high-risk subgroup with the poorest prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10507256251388028","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T15:41:20Z","timestamp":1761234080000},"page":"1268-1276","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Validation of the International Medullary Thyroid Carcinoma Grading System in Patients with Distant Metastases"],"prefix":"10.1177","volume":"35","author":[{"given":"Tommaso","family":"Porcelli","sequence":"first","affiliation":[{"name":"D\u00e9partement d\u2019Imagerie M\u00e9dicale, Gustave Roussy, Service de Canc\u00e9rologie Endocrinienne, Paris-Saclay University, Villejuif, France."},{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Moog","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Imagerie M\u00e9dicale, Gustave Roussy, Service de Canc\u00e9rologie Endocrinienne, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed-Amine","family":"Bani","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biologie et Pathologie M\u00e9dicale, Gustave Roussy, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Hadoux","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Imagerie M\u00e9dicale, Gustave Roussy, Service de Canc\u00e9rologie Endocrinienne, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Bruzzese","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Salvatore","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9sir\u00e9e","family":"Deandreis","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Imagerie M\u00e9dicale, Gustave Roussy, Service de Canc\u00e9rologie Endocrinienne, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schlumberger","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Imagerie M\u00e9dicale, Gustave Roussy, Service de Canc\u00e9rologie Endocrinienne, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Hartl","sequence":"additional","affiliation":[{"name":"D\u00e9partement Anesth\u00e9sie Chirurgie et Interventionnel, Gustave Roussy, Chirurgie des tumeurs ORL\/T\u00eate et cou, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Breuskin","sequence":"additional","affiliation":[{"name":"D\u00e9partement Anesth\u00e9sie Chirurgie et Interventionnel, Gustave Roussy, Chirurgie des tumeurs ORL\/T\u00eate et cou, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba Khazen","family":"Nariman","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Imagerie M\u00e9dicale, Gustave Roussy, Service de Canc\u00e9rologie Endocrinienne, Paris-Saclay University, Villejuif, France."},{"name":"Endocrine Department, Linn Medical Center, Klalit Medical Services, 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