Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8666, Japan.
Lung Cancer. 2011 Feb;71(2):224-8. doi: 10.1016/j.lungcan.2010.05.004.
The purposes of this study were to assess the relationship of serum levels of pro-gastrin-releasing protein (ProGRP) and neuron-specific enolase (NSE) at relapse with survival after relapse and the response to salvage therapy and to assess whether serum levels of ProGRP and NSE at relapse are useful markers for detecting relapse earlier than are symptoms or radiographic findings in patients with small-cell lung cancer (SCLC). The subjects of this study were 103 patients with SCLC who had achieved a complete response (CR) or partial response (PR) to first-line chemotherapy. We retrospectively evaluated whether ProGRP or NSE increased earlier than symptoms or radiographic findings appeared, and the association between response to salvage therapy and levels of ProGRP or NSE at relapse. In addition, we evaluated the association between survival after relapse and clinical and demographic factors at relapse, including age, sex, response to first-line treatment, sensitivity to first-line treatment, stage, performance status (PS), and serum levels of ProGRP, NSE, and lactate dehydrogenase. At relapse, 69.3% of patients had elevated serum levels of ProGRP, 60.2% had elevated serum levels of NSE, and 81.3% had elevated serum levels of either ProGRP or NSE. However, almost all asymptomatic relapses were detected with radiographic studies. The rate of CR to salvage chemotherapy was significantly lower in patients with elevated levels of NSE (2.2%) than in patients without (26.7%; p=0.001). Univariate analysis showed that sensitivity to first-line treatment, serum levels of NSE, stage, and PS at relapse were prognostic factors for survival after relapse. Multivariate analysis showed that sensitivity to first-line treatment, serum levels of NSE, and PS at relapse were independent prognostic factors after relapse. In conclusion, serum levels of ProGRP and NSE at relapse are not useful markers for detecting relapse earlier than are symptoms or radiographic findings. On the other hand, the serum level of NSE at relapse is a useful predictive marker for CR to salvage chemotherapy and a useful prognostic factor after relapse in patients with SCLC who have achieved a CR or PR to first-line chemotherapy.
本研究的目的是评估复发时血清胃泌素释放肽前体（ProGRP）和神经元特异性烯醇化酶（NSE）水平与复发后生存的关系，以及与挽救治疗反应的关系，并评估复发时血清 ProGRP 和 NSE 水平是否比小细胞肺癌（SCLC）患者的症状或影像学发现更早地成为检测复发的有用标志物。本研究的对象是 103 例接受一线化疗后达到完全缓解（CR）或部分缓解（PR）的 SCLC 患者。我们回顾性评估了 ProGRP 或 NSE 是否比症状或影像学发现更早升高，以及挽救治疗反应与复发时 ProGRP 或 NSE 水平之间的关系。此外，我们评估了复发时临床和人口统计学因素（包括年龄、性别、一线治疗反应、对一线治疗的敏感性、分期、体能状态（PS）和血清 ProGRP、NSE 和乳酸脱氢酶水平）与复发后生存之间的关系。在复发时，69.3%的患者血清 ProGRP 水平升高，60.2%的患者血清 NSE 水平升高，81.3%的患者血清 ProGRP 或 NSE 水平升高。然而，几乎所有无症状复发都通过影像学研究检测到。在 NSE 水平升高的患者中，挽救化疗的 CR 率明显低于 NSE 水平正常的患者（2.2%比 26.7%；p=0.001）。单因素分析显示，一线治疗的敏感性、复发时 NSE 血清水平、分期和 PS 是复发后生存的预后因素。多因素分析显示，一线治疗的敏感性、复发时 NSE 血清水平和 PS 是复发后的独立预后因素。总之，复发时血清 ProGRP 和 NSE 水平并不能比症状或影像学发现更早地成为检测复发的有用标志物。另一方面，复发时 NSE 血清水平是接受一线化疗后达到 CR 或 PR 的 SCLC 患者挽救化疗获得 CR 的有用预测标志物，也是复发后的有用预后因素。
