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Elhassan, Y. S.; Altieri, B.; Berhane, S.; Cosentini, D.; Calabrese, A.; Haissaguerre, M.; Kastelan, D.; Fragoso, M. C. B. V.; Bertherat, J.; Al Ghuzlan, A.; Haak, H.; Boudina, M.; Canu, L.; Loli, P.; Sherlock, M.; Kimpel, O.; Lagana, M.; Sitch, A. J.; Kroiss, M.; Arlt, W.; Terzolo, M.; Berruti, A.; Deeks, J. J.; Libe, R.; Fassnacht, M. and Ronchi, C. L. (2022): S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study. In: European Journal of Endocrinology, Vol. 186, No. 1: pp. 25-36

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Objective Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on the European Network for the Study of Adrenal Tumours stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC. Design This is a multicentre, retrospective study on ACC patients who underwent adrenalectomy. Methods The S-GRAS score was calculated as a sum of the following points: tumour stage (1-2 = 0;3 = 1;4 = 2), grade (Ki67 index 0-9% = 0;10-19% = 1;>= 20% = 2 points), resection status (R0 = 0;RX = 1;R1 = 2;R2 = 3), age (<50 years = 0;>= 50 years = 1), symptoms (no = 0;yes = 1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's Concordance index (C-index) and Royston-Sauerbrei's R-D(2) statistic. Results We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index = 0.73, R-D(2) = 0.30, and C-index = 0.79, R-D(2) = 0.45, respectively, all P < 0.01vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n = 481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5. Conclusion The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

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