Assessment of prognostic factors in pediatric adrenocortical tumors: a systematic review and evaluation of a modified S-GRAS score

Abstract

Objective Pediatric adrenocortical carcinoma (pACC) is rare and prognostic stratification remains challenging. We summarized clinical prognostic factors of pACC and determined the prognostic value of the pediatric scoring system (pS-GRAS) in adaption to the recommendation (S-GRAS) of ENSAT for the classification of adult ACC. Design Analysis on pACC patients of 33 available retrospective studies in the literature. Methods We searched the PubMed and Embase databases for manuscripts regarding pACC. PS-GRAS score was calculated as a sum of tumor stage (1=0; 2-3=1; 4=2 points), grade (Ki67 index/rate of mitosis 0-9%/ low=0; 10-19%/ intermediate=1; ≥20%/ high=2 points), resection status (R0=0; RX=1; R1=2; R2=3 points), age (<4 years=0; ≥4 years=1 point), hormone related symptoms (androgen production=0; glucocorticoid-/mixed/-no hormone production=1 point) generating ten scores and four groups (1: 0-2, 2: 3-4, 3: 5, 4: 6-9). Primary endpoint was overall survival (OS). Results We included 733 patients. Median age was 2.5 years and >85% of pACC showed hormone activity (mixed 50%, androgen 29%, glucocorticoid 21%). Androgen production was associated with a superior OS. Increasing age correlated with higher rates of inactive or only glucocorticoid-producing tumors, advanced tumor stage, and case fatality. Especially infants < 4 years showed more often low risk constellations with an increased OS for all tumor stages. The pS-GRAS score correlated with clinical outcome; median OS was 133 months (95%CI: 36-283) in group 1 (n=49), 110 months (95%CI: 2.9-314) in 2 (n=57), 49 months (95%CI: 5.8-278) in group 3 (n=18), and 16 months (95%CI: 2.4-267) in group 4; (n=11) p<0.05). Conclusion PS-GRAS score seems to have a high predictive value in pACC patients, may serve as a helpful tool for risk stratification in future studies and should be evaluated prospectively in an international context

Outcome for Pediatric Adreno-Cortical Tumors Is Best Predicted by the COG Stage and Five-Item Microscopic Score—Report from the German MET Studies

“…It relies on the tumor size, status of resection, and status of metastases. It, thereby, encompasses most clinical prognostic factors in children and adolescents with ACTs [10,13,25,26]. Accordingly, in our study, the COG stage correlated with the outcome (OS COG I 100%, COG II 87.5%, COG III 69.5%, and COG IV 19.7%), confirming previous studies [18,20].…”

“…Age defines the clinical presentation and prognosis in children and adolescents with ACTs [17,19,20,25,26]. Patients aged ≥ 4 years more frequently presented with advanced tumor stages, including distant metastases, compared to younger patients.…”

“…It should not go unmentioned that the score was calculated retrospectively in our study. Based on a systematic review of the literature, Riedmeier and colleagues recently assessed a modified S-GRAS score for pediatric ACTs [25]. The final score encompassed the tumor stage, grade (Ki67 index/rate of mitosis), resection status, age, and hormone-related symptoms.…”

Outcome of brain metastases from adrenocortical carcinoma: a pooled analysis

“…To improve prognostication [ 14 ], the S-GRAS score (tumor Stage—Grade, R status, Age and Symptoms) was introduced in clinical practice, combining the different clinical and histopathological parameters associated with prognosis [ 15 ]. Furthermore, the S-GRAS score was adapted to the pediatric population creating the pediatric scoring system pS-GRAS [ 16 ].…”

Locally Advanced Adrenocortical Carcinoma in Children and Adolescents—Enigmatic and Challenging Cases

“…This two-tier approach was subsequently adopted in the diagnostic and therapeutic recommendations for adrenocortical tumors in children and adolescents of the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) [1]. Recently, Riedmeier and colleagues published a modified (pediatric) S-GRAS score adapted from the European Network for the Study of Adrenal Tumors for prognostic classification of adult ACC [14,15].…”