ECE2020 Oral Communications Adrenal and Cardiovascular Endocrinology (7 abstracts)
Modified GRAS score for prognostic classification of adrenocortical carcinoma: an ENSAT multicentre study
Yasir Elhassan 1 , Barbara Altieri 2 , Sarah Berhane 3 , Harriet Cook 1 , Jerome Bertherat 4 , Maria Fragoso 5 , Darko Kastelan 6 , Massimo Terzolo 7 , Anna Calabrese 7 , Alfredo Berruti 8 , Deborah Cosentini 8 , Marta Laganà 8 , Paola Loli 9 , Eric Baudin 10 , Harm Haak 11 , Letizia Canu 12 , Magalie Haissaguerre 13 , Otilia Kimpel 2 , Jon Deeks 3 , Wiebke Arlt 1 , Rossella Libé 14 , Martin Fassnacht 2 & Cristina Ronchi 1
1Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom; 2Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg, Wuerzburg, Germany; 3Test Evaluation Research Group (TERG), Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom; 4Reference Center for Rare Adrenal Cancer (COMETE), Cochin Hospital, Paris, France; 5Unidade de Suprarrenal da Disciplina de Endocrinologia e Metabologia da Faculdade de Medicina da, Universidade de São Paulo, São Paulo, Brazil; 6Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia; 7University of Turin, Department. of Clinical and Biological Sciences, San Luigi Hospital, Orbassano, Italy; 8Medical Oncology, University of Brescia, ASST-Spedali Civili, Brescia, Italy; 9Clinica Polispecialistica San Carlo, via Ospedale 21, Paderno Dugnano, Milano, Italy; 10Nuclear Medicine and Endocrine Oncology, Gustave Roussy Cancer Center, Paris, France; 11Department of Internal Medicine Máxima MC, Eindhoven, Netherlands; 12Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; 13Service d’Endocrinologie - Diabète et Nutrition CHU de Bordeaux, Bordeaux, France; 14Department of Endocrinology and Metabolic Diseases, Hôpital Cochin, Paris, France
Background: Adrenocortical carcinoma (ACC) has an aggressive but heterogenous behaviour. ENSAT stage and Ki67 proliferation index are used to predict clinical outcome but are limited in distinguishing patients with best outcome. We aimed to validate the prognostic role of clinical and histopathological parameters alone or combined by applying a previously proposed points-based score (mGRAS, Lippert JCEM 2018) to a large multicentre cohort of ACC patients.
Methods: International multicentre retrospective study including ACC patients who underwent adrenalectomy from 2010–2019. Acquired covariates include age at diagnosis, presence of steroid- or mass-related symptoms, ENSAT stage, tumour resection status, Ki67, progression-free survival (PFS), and disease-specific survival (DSS). Each parameter’s prognostic value was tested by univariable analysis and PFS and DSS were the primary and secondary endpoints, respectively. Additionally, we evaluated the prognostic performance of mGRAS calculated as follows: age ( < 50 yr = 0 ≥ 50 yr = 1), symptoms (no = 0; yes = 1), ENSAT stage (1–2 = 0; 3 = 1; 4 = 2), resection status (R0 = 0; RX = 0.5; R1 = 1; R2 = 2), and Ki67 (0–9% = 0; 10–19% = 1; ≥20% = 2 points), generating four mGRAS groups: 0–1, 2–3, 4–5, and 6–9. Survival curves were plotted via the Kaplan-Meier method. The discriminative performance of mGRAS and its components were compared using the Harrell’s C-index and Royston-Sauerbrei’s R2D statistic.
Results: We screened 1075 patients from 14 centres; 946 patients met the inclusion criteria (median age 50 years; 61.9% females). Univariable cox regression showed that mGRAS and its components significantly influenced both PFS and DSS. With PFS, mGRAS showed superior prognostic discrimination (C-index 0.71, R2D 0.29) compared to its components: symptoms (C-index 0.57, R2D 0.08), ENSAT stage (C-index 0.67, R2D 0.21), resection status (C-index 0.60, R2D 0.18), and Ki67 (C-index 0.65, R2D 0.21). mGRAS divided the cohort into four groups with median PFS of 181.6, 33.0, 9.8, and 6.0 months. Similarly, with DSS, mGRAS showed superior discrimination (C-index 0.76, R2D 0.44) compared to symptoms (C-index 0.60, R2D 0.15), ENSAT stage (C-index 0.72, R2D 0.35), resection status (C-index 0.64, R2D 0.25), and Ki67 (C-index 0.68, R2D 0.31). Median DSS for the mGRAS groups were 248.8, NR, 66.0, and 18.1 months.
Conclusion: The prognostic performance of mGRAS is superior to that of individual clinical and histopathological parameters. This simple score will be valuable in guiding personalised treatment decisions in patients with ACC, e.g. the need for adjuvant mitotane and frequency of monitoring.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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