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Maria Riedmeier, Boris Decarolis, Imme Haubitz, Joachim Reibetanz, Armin Wiegering, Christoph Härtel, Paul-Gerhardt Schlegel, Martin Fassnacht, and Verena Wiegering

Objective

Pediatric adrenocortical carcinoma (pACC) is rare and prognostic stratification remains challenging. We summarized the 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 the European Network for the Study of Adrenal Tumors for the classification of adult ACC.

Design

Analysis of pACC patients of 33 available retrospective studies in the literature.

Methods

We searched the PubMed and Embase databases for manuscripts regarding pACC. The 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 10 scores and 4 groups (1: 0–2, 2: 3–4, 3: 5, 4: 6–9). The primary endpoint was overall survival (OS).

Results

We included 733 patients. The 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 group 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

The pS-GRAS score seems to have a high predictive value in the pACC patients, may serve as a helpful tool for risk stratification in future studies, and should be evaluated prospectively in an international context.