{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:56:25Z","timestamp":1785297385543,"version":"3.55.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"GETTHI"},{"name":"SEEN"},{"name":"Esteve-HRA Pharma Rare Diseases"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with variable outcomes post-adrenalectomy. The S-GRAS score integrates 5 clinical and pathological factors to predict prognosis but requires external validation in diverse settings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We validated the S-GRAS score in 138 ACC patients from the Spanish ICARO-GETTHI\/SEEN registry (1998-2023). Model performance was assessed using discrimination, calibration, and accuracy. Exploratory refinements included non-linear modeling of age and Ki-67% and an expanded model incorporating venous invasion and tumor size. Cox models examined the interaction between S-GRAS and adjuvant mitotane.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 76 recurrence events were recorded. The S-GRAS score demonstrated good discrimination for overall survival (C-index 0.706, 95% CI, 0.628-0.785) and recurrence-free survival (C-index 0.673, 95% CI, 0.601-0.745) with well-calibrated predictions. Five-year survival rates differed significantly across score groups: 100% for scores 0-1, 81.6% for 2-3, 55% for 4-5, and 33.8% for 6-7. Non-linear modeling of Ki-67% improved performance (C-index 0.738 for RFS, 0.761 for OS), but adding clinical variables offered minimal benefit, leaving 75% of recurrence variability unexplained. Higher S-GRAS scores correlated with increased mitotane benefit (HR 0.57, 95% CI, 0.34-0.97 for score 4; HR 0.46, 95% CI, 0.23-0.94 for score 5), indicating a potential incremental benefit pattern.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings validate the S-GRAS score in a multicenter cohort and support its use in identifying candidates for adjuvant mitotane. Non-linear modeling of Ki-67% enhances predictive precision without increasing complexity, but the performance plateau of clinical variables suggests that integrating molecular biomarkers may be necessary to improve prognostic accuracy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf171","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T16:06:11Z","timestamp":1756224371000},"page":"320-328","source":"Crossref","is-referenced-by-count":1,"title":["External validation of the S-GRAS score for predicting recurrence in patients with adrenocortical carcinoma: implications for adjuvant mitotane therapy"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4592-3813","authenticated-orcid":false,"given":"Paula","family":"Jimenez-Fonseca","sequence":"first","affiliation":[{"name":"Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA , Oviedo, 33011 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