OC31 - Prognostic value of serum inflammation-based scores in localized adrenocortical carcinoma undergoing adjuvant mitotane therapy: a multicenter ENSAT study

Background Mitotane monotherapy is the standard adjuvant treatment for adrenocortical carcinoma (ACC), yet reliable predictors of treatment response remain lacking. Given the well-recognized interplay between inflammation and cancer progression, serum inflammation-based scores have shown prognostic significance in various malignancies, including ACC in palliative settings. However, their relevance during adjuvant mitotane therapy remains uncertain. This study aimed to assess the prognostic value of inflammation-scores in patients with ACC receiving adjuvant mitotane. Methods Multicenter ENSAT retrospective study including patients with ACC treated with adjuvant mitotane as first-line therapy. Clinical data including age, sex, ENSAT tumor stage, Ki67 index, resection status, and hormone secretion were collected at diagnosis. Inflammation-scores - neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), systemic immune inflammation index (SII), and pan-immune-inflammation value (PIV) - were calculated at diagnosis (pre-surgery) and at mitotane start. Median values of inflammation-scores at diagnosis defined low and high levels. Overall survival (OS) and time to progression (TTP) from mitotane start were the primary endpoints. Results The study included 395 patients (66% female; median age: 51 years). Median time to mitotane start was 54 days (IQR: 32–90). At diagnosis, patients with glucocorticoid excess (n=84) had significantly higher inflammation-scores than those without (n=104): NLR (3.61 vs 2.53), dNLR (2.31 vs 1.72), SII (864.1 vs 679.3), and PIV (531.6 vs 343.1); all p≤0.005. All scores significantly declined after surgery (p<0.05). Higher inflammatory scores at diagnosis were associated with worse OS (NLR: HR=3.85, 95%CI=1.95–7.59, p<0.001; dNLR: HR=3.19, 95%CI=1.67- 6.08, p<0.001; SII: HR=1.97, 95%CI = 1.07–3.61, p=0.03; PIV: HR=2.11, 95%CI=1.13-3.95, p=0.02). However, only the NLR and dNLR remained independently associated with OS at multivariate analysis adjusted for ENSAT stage, Ki67 index, and resection status (p<0.05). At mitotane start (n=372), high SII and PIV were associated with shorter TTP (SII: HR=1.36, 95%CI=1.02-1.82, p=0.03; PIV: HR=1.40, 95%CI=1.04-1-87, p=0.02), with only SII remaining significant at multivariate regression (p=0.04). Conclusions Inflammation-based scores are higher in patients with glucocorticoid excess and decrease postoperatively. NLR and dNLR at diagnosis, and SII at mitotane start, are associated with clinical outcomes in patients with ACC receiving mitotane adjuvant monotherapy. These readily available markers may help improve prognostic stratification in clinical practice.