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

Elhassan, Yasir S; Altieri, Barbara; Berhane, Sarah; Cosentini, Deborah; Calabrese, Anna; Haissaguerre, Magalie; Kaštelan, Darko; Fragoso, Maria Candida Barisson Villares; Bertherat, Jérôme; Ghuzlan, A. Al; Haak, Harm R.; Boudina, Maria; Canu, Letizia; Loli, Paola; Sherlock, Mark; Kimpel, Otilia; Laganà, Marta; Sitch, Alice; Kroiß, Matthias; Arlt, Wiebke; Terzolo, Massimo; Berruti, Alfredo; Deeks, Jonathan J; Libé, Rossella; Fassnacht, Martin; Ronchi, Cristina L.

doi:10.1530/eje-21-0510

Cited by 57 publications

(52 citation statements)

References 43 publications

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“…The recently validated S-GRAS (Stage, Grade based on the Ki67 labeling index, Resection status and Symptoms) scoring scheme has shown a better prognostic significance compared to the tumor stage and Ki67 proliferation index in patients with adrenal cortical carcinomas [ 169 ]. The Ki67 proliferation index is a component of the Helsinki scoring system that uses the proliferation index as a continuous numeric value [ 132 ].…”

Section: Question 9: What Is the Role Of Mitotic Tumor Grade And The ...mentioning

confidence: 99%

Overview of the 2022 WHO Classification of Adrenal Cortical Tumors

et al. 2022

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The new WHO classification of adrenal cortical proliferations reflects translational advances in the fields of endocrine pathology, oncology and molecular biology. By adopting a question–answer framework, this review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the adrenal cortex pathologies that are now reflected in the 2022 WHO classification. The pathological correlates of adrenal cortical proliferations include diffuse adrenal cortical hyperplasia, adrenal cortical nodular disease, adrenal cortical adenomas and adrenal cortical carcinomas. Understanding germline susceptibility and the clonal-neoplastic nature of individual adrenal cortical nodules in primary bilateral macronodular adrenal cortical disease, and recognition of the clonal-neoplastic nature of incidentally discovered non-functional subcentimeter benign adrenal cortical nodules has led to redefining the spectrum of adrenal cortical nodular disease. As a consequence, the most significant nomenclature change in the field of adrenal cortical pathology involves the refined classification of adrenal cortical nodular disease which now includes (a) sporadic nodular adrenocortical disease, (b) bilateral micronodular adrenal cortical disease, and (c) bilateral macronodular adrenal cortical disease (formerly known primary bilateral macronodular adrenal cortical hyperplasia). This group of clinicopathological entities are reflected in functional adrenal cortical pathologies. Aldosterone producing cortical lesions can be unifocal or multifocal, and may be bilateral with no imaging-detected nodule(s). Furthermore, not all grossly or radiologically identified adrenal cortical lesions may be the source of aldosterone excess. For this reason, the new WHO classification endorses the nomenclature of the HISTALDO classification which uses CYP11B2 immunohistochemistry to identify functional sites of aldosterone production to help predict the risk of bilateral disease in primary aldosteronism. Adrenal cortical carcinomas are subtyped based on their morphological features to include conventional, oncocytic, myxoid, and sarcomatoid subtypes. Although the classic histopathologic criteria for diagnosing adrenal cortical carcinomas have not changed, the 2022 WHO classification underscores the diagnostic and prognostic impact of angioinvasion (vascular invasion) in these tumors. Microscopic angioinvasion is defined as tumor cells invading through a vessel wall and forming a thrombus/fibrin-tumor complex or intravascular tumor cells admixed with platelet thrombus/fibrin. In addition to well-established Weiss and modified Weiss scoring systems, the new WHO classification also expands on the use of other multiparameter diagnostic algorithms (reticulin algorithm, Lin–Weiss–Bisceglia system, and Helsinki scoring system) to assist the workup of adrenal cortical neoplasms in adults. Accordingly, conventional carcinomas can be assessed using all multiparameter diagnostic scheme...

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Section: Question 9: What Is the Role Of Mitotic Tumor Grade And The ...mentioning

confidence: 99%

Overview of the 2022 WHO Classification of Adrenal Cortical Tumors

et al. 2022

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“…The other forecasting methodology is the GRAS parameter, which includes the grade (Ki67 index), resection status, age, and symptoms caused by tumors or hormone secretion. The recently proposed S-GRAS score system combines the GRAS parameter and ENSAT stage ( 9 ), where the latter is a classical method for predicting the prognosis of ACC, although it was not confirmed as an independent predictor in several cohorts ( 17 , 18 ). Ki67 and the resection status have been consistently recognized as factors with significant prognostic power in most studies, although an interobserver variation of Ki67 was found in previous studies ( 9 , 18 , 19 ).…”

Section: Discussionmentioning

confidence: 99%

“…Survival data, causes of death, and postoperative treatment were collected through outpatient clinical visits or by telephone. The S-GRAS score was calculated as a sum of the following points: tumor 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 categorization, which generated four groups (0–1, 2–3, 4–5, and 6–9) ( 9 ).…”

Section: Methodsmentioning

confidence: 99%

“…Several models, which were developed from the Surveillance, Epidemiology, and End Results (SEER) database comprising more than 1000 ACC patients, have shown promising predictive accuracy in American patients ( 5 , 7 , 8 ). Recently, a scoring system known as the S-GRAS score has been developed from a multicenter cohort comprising 942 patients from the European Network for the Study of Adrenal Tumors (ENSAT) group ( 9 , 10 ). These tools focus on different clinical variables, but no comparison has been made in the same cohort.…”

Section: Introductionmentioning

confidence: 99%

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S-GRAS score performs better than a model from SEER for patients with adrenocortical carcinoma

Lin

Dai

Xie

et al. 2022

Endocrine Connections

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Purpose: To externally validate the performance of the S-GRAS score and a model from the SEER database in a Chinese cohort of patients with adrenocortical carcinoma (ACC). Methods: We first developed a model using data from the SEER database, after which we retrospectively reviewed 51 ACC patients hospitalized between 2013 and 2018, and we finally validated the model and S-GRAS score in this Chinese cohort. Results: Patient age at diagnosis, tumor size, TNM stage, and radiotherapy were used to construct the model, and the Harrell’s C-index of the model in the training set was 0.725 (95%CI: 0.682-0.768). However, the 5-year AUC of the model in the validation cohort was 0.598 (95%CI: 0.487-0.708). The 5-year AUC of the ENSAT stage was 0.640 (95%CI: 0.543-0.737), but the Kaplan-Meier curves of stage I and II overlapped in the validation cohort. The resection status (P=0.066), age (P=0.68), Ki67 (P=0.69), and symptoms (P=0.66) did not have a significant impact on cancer-specific survival in the validation cohort. In contrast, the S-GRAS score group showed better discrimination (5-year AUC: 0.683, 95%CI: 0.602-0.764) than the SEER model or the ENSAT stage. Conclusion: The SEER model showed favorable discrimination and calibration ability in the training set, but it failed to distinguish patients with various prognoses in our institution. In contrast, the S-GRAS score could effectively stratify patients with different outcomes.

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“…The disease stage according to modified European Network for the Study of Adrenal Tumors (mENSAT) classification, 26 tumor Grade, Resection status, Age of patients and presence of Symptoms at ACC diagnosis (accordigly to the GRAS parameters), 27 , 28 resection status of the primary tumor, and previous ACC-correlated medical and surgical treatments were collected.…”

Section: Methodsmentioning

confidence: 99%