RESUMO
BACKGROUND: Serum inflammation-based scores can predict clinical outcome in several cancer types, including adrenocortical carcinoma (ACC). It is unclear whether the extent of inflammation-based scores alterations in ACC reflects malignancy, steroid excess, or both. METHODS: We investigated a large retrospective cohort of adrenocortical adenomas (ACA, n = 429) and ACC (n = 61) with available baseline full blood count and hormonal evaluation. We examined the relationship between different inflammation-based scores [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI)] and both malignancy and steroid secretion patterns. RESULTS: All inflammation-based scores differed between ACC and ACA: patients with ACC had higher NLR, PLR, SII and lower LMR and PNI levels compared to ACA (all p values < 0.001). NLR showed a positive correlation with cortisol levels after overnight 1 mg-dexamethasone suppression test (1 mg-DST), both in ACC and ACA (p < 0.01). The ROC curve analysis determined NLR > 2.6 as the best cut-off to discriminate ACC from ACA [AUC = 0.846, p < 0.01]. At multivariable analysis, NLR > 2.6 was independently associated with ACC, 1 mg-DST cortisol levels and age, but not with tumour size. Considering the ACC, NLR and SII were higher and PNI was lower in patients with cortisol excess compared to those without cortisol excess (p = 0.002, p = 0.007, and p = 0.044 respectively). Finally, LMR and NLR differed between inactive-ACC (n = 10) and inactive-ACA (n = 215) (p = 0.040 and p = 0.031, respectively). CONCLUSION: Inflammation-based scores are related to steroid secretion both in ACC and ACA. ACCs present a higher grade of inflammation regardless of their hormonal secretion, likely as a feature of malignancy itself.
RESUMO
OBJECTIVE: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on the European Network for the Study of Adrenal Tumours stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC. DESIGN: This is a multicentre, retrospective study on ACC patients who underwent adrenalectomy. METHODS: The S-GRAS score was calculated as a sum of the following points: tumour 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 categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's Concordance index (C-index) and Royston-Sauerbrei's R2D statistic. RESULTS: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index = 0.73, R2D = 0.30, and C-index = 0.79, R2D = 0.45, respectively, all P < 0.01vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n = 481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5. CONCLUSION: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).
