-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT stud

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Elhassan, Y. S. ^{[1, 2]} ; Altieri, B. ^[3] ; Berhane, S. ^{[4, 5, 6]} ; Cosentini, D. ^[7] ; Calabrese, A. ^[8] ; Haissaguerre, M. ^[9] ; Kastelan, D. ^[10] ; Fragoso, V, M. C. B. ; Bertherat, J. ^[11] ; Al Ghuzlan, A. ^[12] ; Haak, H. ^[13] ; Boudina, M. ^[14] ; Canu, L. ^[15] ; Loli, P. ^[16] ; Sherlock, M. ^{[17, 18]} ; Kimpel, O. ^[3] ; Lagana, M. ^[7] ; Sitch, A. J. ^{[4, 5, 6]} ; Kroiss, M. ^{[19, 3, 20]} ; Arlt, W. ^{[4, 1, 2, 6]} ; Terzolo, M. ^[8] ; Berruti, A. ^[7] ; Deeks, J. J. ^{[4, 5, 6]} ; Libe, R. ^[21] ; Fassnacht, M. ^{[19, 3]} ; Ronchi, C. L. ^{[1, 2, 3]} ; ENSAT

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^[1] Univ Birmingham, Inst Metab & Syst Res, Birmingham, W Midlands - England

^[2] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Dept Endocrinol, Birmingham, W Midlands - England

^[3] Univ Wurzburg, Univ Hosp, Dept Internal Med 1, Div Endocrinol & Diabet, Wurzburg - Germany

^[4] Univ Birmingham, Birmingham, W Midlands - England

^[5] Univ Birmingham, Inst Appl Hlth Res, Birmingham, W Midlands - England

^[6] Univ Hosp Birmingham NHS Fdn Trust, NIHR Birmingham Biomed Res Ctr, Birmingham, W Midlands - England

^[7] Radiol Sci & Publ Hlth Univ Brescia, Dept Med & Surg Specialties, Med Oncol, ASST Spedali Civili, Brescia - Italy

^[8] Univ Turin, San Luigi Hosp, Dept Clin & Biol Sci, Orbassano - Italy

^[9] CHU Bordeaux, Serv Endocrinol Diabet & Nutr, Bordeaux - France

^[10] Univ Hosp Ctr Zagreb, Dept Endocrinol, Zagreb - Croatia

^[11] Cochin Hosp, Reference Ctr Rare Adrenal Canc COMETE, Paris - France

^[12] Gustave Roussy Canc Ctr, Dept Pathol, Paris - France

^[13] Maxima MC, Dept Internal Med, Eindhoven - Netherlands

^[14] Theagenio Canc Hosp, Dept Endocrinol, Thessaloniki - Greece

^[15] Univ Florence, Dept Expt & Clin Biomed Sci, Florence - Italy

^[16] Clin Polispecialist San Carlo, Milan - Italy

^[17] Beaumont Hosp, Dept Endocrinol, Dublin - Ireland

^[18] Royal Coll Surg, Dublin - Ireland

^[19] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, Wurzburg - Germany

^[20] Ludwig Maximilians Univ Munchen, Dept Endocrinol, Med Klin & Poliklin 4, Munich - Germany

^[21] Hop Cochin, Dept Endocrinol & Metab Dis, Paris - France

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 186, n. 1, p. 25-36, JAN 1 2022.
• Citações Web of Science: 0

Resumo

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). (AU)

• Processo FAPESP: 17/26345-5 - Avaliação de fatores prognósticos dos tumores do córtex da suprarrenal e preditivos da resposta ao tratamento com mitotano em carcinomas
• Beneficiário: Maria Candida Barisson Villares Fragoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular