title: Synchronous vs. Metachronous Metastases in Adrenocortical Carcinoma: an Analysis of the Dutch Adrenal Network.
abstract: Adrenal Cortical Carcinoma (ACC) is a rare malignancy with an incidence of 1.0 per million per year in the Netherlands. Median survival varies according to the European Network for the Study of Adrenal Tumours (ENS@T) tumour stage. It is unknown whether time until development of metastases is of influence on prognosis. To asses this, data were retrospectively obtained from centres of the Dutch Adrenal Network. Patients who presented with ACC between January 1, 2004 and October 31, 2013 were included. Date of detection of metastases, number of metastases and affected organs were registered. One hundred sixty patients were included in the analysis. Synchronous metastases were defined as diagnosis of metastasis ≤6 months after the initial diagnosis of ACC. Overall survival rate was calculated from the date of diagnosis of metastasis until death from any cause. At first presentation, 50 patients (31 %) had ACC with metastases (ENS@T stage IV). Another 67 (42 %) developed metastases during follow-up. Amongst the 117 patients with metastases, 84 (72 %) patients had synchronous metastases and 33 (28 %) developed metachronous metastases. Diagnosis of synchronous metastases (p = 0.046), more than one affected organ (p < 0.001) and four or more metastases (p < 0.001) were found to be associated with reduced overall survival. Limitations included retrospective design and limited details regarding pathological data. We conclude that synchronous metastases of ACC are associated with a poorer prognosis compared to metachronous metastases of ACC. The clinical characteristics associated with prognosis in this study support the view to refine the prognostic classification for patients with stage IV ACC.
authors.affiliation: Department of Internal Medicine, Department of Endocrinology, Máxima Medical Centre, Ds. Th. Fliednerstraat 1, 5631 BM, Eindhoven/Veldhoven, The Netherlands. h.ettaieb@mmc.nl.
authors.forename: M H T
authors.initials: MH
authors.lastname: Ettaieb
authors.affiliation: Department of Internal Medicine, Department of Endocrinology, Máxima Medical Centre, Ds. Th. Fliednerstraat 1, 5631 BM, Eindhoven/Veldhoven, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Duker
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Feelders
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Leiden Medical Centre, Leiden, The Netherlands.
authors.forename: E P M
authors.initials: EP
authors.lastname: Corssmit
authors.affiliation: Department of Medical Oncology, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: C W
authors.initials: CW
authors.lastname: Menke-van der Houven van Oordt
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: H J L M
authors.initials: HJ
authors.lastname: Timmers
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: M N
authors.initials: MN
authors.lastname: Kerstens
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Wilmink
authors.affiliation: Department of Internal Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Zelissen
authors.affiliation: Department Internal Medicine, Division of Endocrinology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Havekes
authors.affiliation: Department of Internal Medicine, Department of Endocrinology, Máxima Medical Centre, Ds. Th. Fliednerstraat 1, 5631 BM, Eindhoven/Veldhoven, The Netherlands.|Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.|CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht, The Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Haak
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000401:mortality / Q000473:pathology*; D018268:Adrenocortical Carcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology* / Q000556:secondary; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000556:secondary; D009426:Netherlands; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult