Endocrine Abstracts

Background: Standard treatment for advanced adrenocortical carcinoma (ACC) is mitotane in monotherapy or combined with etoposide, doxorubicin and cisplatin (EDP), yet biomarkers predictive of treatment response are lacking. Inflammation-based scores were proposed as predictors for gemcitabine+capecitabine efficacy, used as second-line in progressive ACC. We investigated the role of inflammation-based scores in predicting response to first-line treatment in advanced ACC.

Methods: Retrospective analysis of patients with advanced ACC treated with mitotane monotherapy or EDP±mitotane. We investigated clinical parameters (ENSAT stage at diagnosis, Ki67, resection-status, time from diagnosis to start treatment, ECOG performance status, plasma mitotane levels and time in mitotane target ≥80%) and pretreatment inflammation-based scores [neutrophil-to-lymphocyte-ratio (NLR), platelet-to-lymphocyte-ratio (PLR), monocyte-to-lymphocyte-ratio (MLR)]. Primary endpoints were time-to-progression (TTP) and overall-survival (OS) from treatment initiation.

Results: We included 64 patients (58% women, median age 52 years); 35 treated with mitotane and 29 with EDP±mitotane. Median TTP was 4 months (range 1-96) and 3 months (1-6), while OS was 14 months (3-133) and 9 months (1-39), respectively. In the mitotane cohort, NLR≥5 predicted significantly shorter TTP (HR 2.86, 95%CI 1.33-6.14) and OS (HR 4.99, 95%CI 2.15-11.61), while PLR≥190 correlated with shorter OS (HR 4.31, 95%CI 1.83-10.19). These findings remained significant at multivariable analysis including Ki67, resection-status, ENSAT stage, ECOG status, time-to-treatment and time in mitotane target (HR 66.55, P=0.02). In the EDP cohort, NLR≥5 and PLR≥190 predicted significantly shorter OS (HR 2.98, 95%CI 1.25-7.09; HR 2.30, 95%CI 1.01-5.25, respectively). Moreover, MLR≥0.4 was associated with worse TTP (HR 3.28, 95%CI 1.17-9.18). However, trends in the EDP cohort were no longer observed at multivariable analyses.

Conclusion: Inflammation-based scores are readily available in clinical practice and may be useful to predict response to first-line pharmacotherapy in patients with advanced ACC. These findings will be validated in larger cohorts.