Assessment of prognostic factors in pediatric adrenocortical tumors: the modified pediatric S-GRAS score in an international multicenter cohort—a work from the ENSAT-PACT working group

Abstract

Objective Pediatric adrenocortical carcinoma (pACC) is rare, and prognostic stratification remains challenging. We aimed to confirm the prognostic value of the previously published pediatric scoring system (pS-GRAS) in an international multicenter cohort. Design Analysis of pS-GRAS items of pACC from six countries in collaboration of ENSAT-PACT, GPOH-MET and IC-PACT. Methods We received patient data of the pS-GRAS items including survival information from nine centers. PS-GRAS score was calculated as a sum of tumor stage (1 = 0; 2–3 = 1; 4 = 2 points), grade (Ki67 index: 0–9%=0; 10–19%=1; ≥ 20%=2 points), resection status (R0 = 0; RX/R1/R2 = 1 point), age (<4 years = 0; ≥ 4 years = 1 point), and hormone production (androgen production = 0; glucocorticoid-/mixed/-no hormone production = 1 point) generating eight scores and four groups (1: 0–2, 2: 3–4, 3: 5, 4: 6–7). Primary endpoint was overall survival (OS). Results We included 268 patients with median age of 4 years. The analysis of the pS-GRAS score showed a significantly favorable prognosis in patients with a lower scoring compared to higher scoring groups (5-year OS: group 1 98%; group 2 87%(HR of death 3.6, 95% CI of HR 1.6-8.2); group 3 43%(HR of death 2.8, 95% CI 1.9–4.4); group 4: OS 18%(HR of death 2.1, 95% CI 1.7-2.7)). In the multivariable analysis age (HR of death 3.5, 95% CI 1.8-7.0), resection status (HR of death 5.5, 95% CI 2.7-11.1), tumor stage (HR of death 1.9, 95%-CI of HR 1.2-3.0) and Ki67-index (HR of death 1.7, 95% CI 1.2-2.4) remained strong independent outcome predictors. Especially infants < 4 years showed more often low risk constellations with a better OS for all tumor stages. Conclusion In an international multicenter study, we confirmed that the pS-GRAS score is strongly associated with overall survival among patients with pACC. Age, resection status, stage and Ki67-index are important parameters for risk stratification.