血清 LDH 水平在索拉非尼治疗 HCC 患者中的预后预测作用：对临床管理的启示。

BACKGROUND: In many tumour types serumlactate dehydrogenase (LDH) levels proved to represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis. As we previously reported LDH is an important predictive factor in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). Sorafenib represents the therapeutic stronghold in advanced HCC patients. As a tyrosine kinase inhibitor (TKI) mainly directed against the angiogenetic pathway, the correlation of sorafenib administration with markers of hypoxia could be an important tool in patients management. Aim of our analysis was to evaluate the role of LDH pre-treatment levels and its variation during treatment in HCC patients receiving sorafenib. METHODS: 78 patients were available for our analysis. For all patients LDH values were collected within one month before the start of treatment and after the end of therapy. For study purposes we divided our patients into two groups, according to LDH pre-treatment levels, cut-off levels was determined with ROC curve analysis. Patients were, also, classified according to the variation in LDH serum levels pre- and post-treatment (increased vs decreased). RESULTS: Patients proved homogeneous for all clinical characteristics analyzed. In patients with LDH values under the cut-off median progression free survival (PFS) was 6.7 months, whereas it was 1.9 months in patients above the cut-off (p = 0.0002). Accordingly median overall survival (OS) was 13.2 months and 4.9 months (p = 0.0006). In patients with decreased LDH values after treatment median PFS was 6.8 months, and median OS was 21.0 months, whereas PFS was 2.9 months and OS 8.6 months in patients with increased LDH levels (PFS: p = 0.0087; OS: p = 0.0035). CONCLUSIONS: In our experience, LDH seemed able to predict clinical outcome in terms of PFS and OS for HCC patients treated with sorafenib. Given the correlation between LDH levels and tumour angiogenesis we can speculate that patients with high LDH pretreatment levels may be optimal candidates for other emerging therapeutic agents or strategies targeting different molecular pathways.

背景：在许多肿瘤类型中，血清乳酸脱氢酶（LDH）水平被证明是肿瘤缺氧、新生血管生成和预后不良的间接标志物。正如我们之前报道的，LDH 是接受经动脉化疗栓塞（TACE）的肝细胞癌（HCC）患者的重要预测因素。索拉非尼是晚期 HCC 患者的治疗支柱。作为一种主要针对血管生成途径的酪氨酸激酶抑制剂（TKI），索拉非尼给药与缺氧标志物的相关性可能是患者管理的重要工具。我们分析的目的是评估 HCC 患者接受索拉非尼治疗前 LDH 水平及其治疗过程中的变化的作用。

方法：78 例患者可用于我们的分析。所有患者在治疗开始前一个月内和治疗结束后收集 LDH 值。出于研究目的，我们根据 LDH 治疗前水平将患者分为两组，通过 ROC 曲线分析确定截断值。根据治疗前和治疗后 LDH 血清水平的变化（升高与降低），患者也进行分类。

结果：患者在所有分析的临床特征方面均表现出均一性。在 LDH 值低于截断值的患者中，无进展生存期（PFS）为 6.7 个月，而 LDH 值高于截断值的患者为 1.9 个月（p = 0.0002）。相应的总生存期（OS）分别为 13.2 个月和 4.9 个月（p = 0.0006）。在治疗后 LDH 值降低的患者中，中位 PFS 为 6.8 个月，中位 OS 为 21.0 个月，而 LDH 值升高的患者中位 PFS 为 2.9 个月，中位 OS 为 8.6 个月（PFS：p = 0.0087；OS：p = 0.0035）。

结论：根据我们的经验，LDH 似乎能够预测接受索拉非尼治疗的 HCC 患者的 PFS 和 OS 临床结局。鉴于 LDH 水平与肿瘤血管生成之间的相关性，我们可以推测，LDH 预处理水平较高的患者可能是针对不同分子途径的其他新兴治疗药物或策略的最佳候选者。