Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Endocr Relat Cancer. 2023 Mar 15;30(4). doi: 10.1530/ERC-22-0372. Print 2023 Apr 1.
Treatment for advanced adrenocortical carcinoma (ACC) consists of mitotane alone or combined with etoposide, doxorubicin, and cisplatin (EDP). Although both therapies are widely used, markers of response are still lacking. Since inflammation-based scores have been proposed as prognostic factors in ACC, we aimed to investigate their role in predicting the response to first-line chemotherapy. We performed a retrospective analysis of patients with advanced ACC treated with mitotane monotherapy or EDP ± mitotane. Clinical parameters (tumour stage at diagnosis, resection status, Ki67, time from diagnosis to treatment start, performance status, plasma mitotane levels, time in mitotane target ≥ 80%, clinically overt cortisol hypersecretion), and pretreatment inflammation-based scores (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, derived neutrophil-to-lymphocyte ratio) were investigated. The primary endpoints were overall survival (OS) and time-to-progression (TTP) from treatment initiation, the secondary endpoint was the best objective response to treatment. We included 90 patients (59% = women, median age = 51 years) treated with mitotane monotherapy (n = 40) or EDP ± mitotane (n = 50). In the mitotane monotherapy cohort, NLR ≥ 5 and PLR ≥ 190 predicted shorter OS (hazard ratio (HR): 145.83, 95% CI: 1.87-11,323.83; HR: 165.50, 95% CI: 1.76-15,538.04, respectively), remaining significant at multivariable analysis including clinical variables. NLR was also associated with shorter TTP (HR: 2.58, 95% CI: 1.28-5.20), but only at univariable analysis. Patients with NLR ≥ 5 showed a worse treatment response than those with NLR < 5 (P = 0.040). In the EDP ± mitotane cohort, NLR ≥ 5 predicted shorter OS (HR: 2.52, 95% CI: 1.30-4.88) and TTP (HR: 1.95, 95% CI: 1.04-3.66) at univariable analysis. In conclusion, inflammation-based scores, calculated from routinely measured parameters, may help predict response to chemotherapy in advanced ACC.
治疗晚期肾上腺皮质癌（ACC）包括单独使用米托坦或联合依托泊苷、多柔比星和顺铂（EDP）。尽管这两种治疗方法都被广泛应用，但仍缺乏反应标志物。由于基于炎症的评分已被提出作为 ACC 的预后因素，我们旨在研究它们在预测一线化疗反应中的作用。我们对接受米托坦单药治疗或 EDP ± 米托坦治疗的晚期 ACC 患者进行了回顾性分析。临床参数（诊断时的肿瘤分期、切除状态、Ki67、从诊断到治疗开始的时间、表现状态、血浆米托坦水平、米托坦目标值达到≥80%的时间、临床明显的皮质醇分泌过多）和治疗前基于炎症的评分（中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、单核细胞与淋巴细胞比值、衍生中性粒细胞与淋巴细胞比值）进行了研究。主要终点是从治疗开始的总生存期（OS）和无进展生存期（TTP），次要终点是治疗的最佳客观反应。我们纳入了 90 名患者（59%=女性，中位年龄=51 岁），其中 40 名接受米托坦单药治疗，50 名接受 EDP ± 米托坦治疗。在米托坦单药治疗组中，NLR≥5 和 PLR≥190 预测 OS 更短（风险比（HR）：145.83，95%CI：1.87-11,323.83；HR：165.50，95%CI：1.76-15,538.04），在包括临床变量的多变量分析中仍然显著。NLR 也与 TTP 更短相关（HR：2.58，95%CI：1.28-5.20），但仅在单变量分析中。NLR≥5 的患者治疗反应比 NLR<5 的患者差（P=0.040）。在 EDP ± 米托坦组中，NLR≥5 预测 OS 更短（HR：2.52，95%CI：1.30-4.88）和 TTP 更短（HR：1.95，95%CI：1.04-3.66），在单变量分析中。总之，基于炎症的评分，由常规测量的参数计算得出，可能有助于预测晚期 ACC 对化疗的反应。
