Department of Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Clin Lung Cancer. 2010 Jan;11(1):36-44. doi: 10.3816/CLC.2010.n.006.
Recent progress in the field of anticancer drug discovery has created many options for improving the survival of patients with cancer. However, more effective diagnostic tools indicating early therapeutic efficacy or disease progression are still needed to improve the management of patients with inoperable cancer.
Plasma nucleosome levels were quantified in 134 patients with advanced non-small-cell lung cancer before the first cycle of chemotherapy. It was also evaluated before the second and third cycles of chemotherapy in 42 patients receiving first-line chemotherapy. Nucleosomes were correlated with response to therapy as assessed by computed tomography after the third therapy cycle.
Patients who went into remission had significantly lower nucleosome levels before therapy cycles 2 and 3 than patients with no change or progression. High levels and insufficient decreases in nucleosome levels during the course of chemotherapy indicated poor outcome. Nucleosome levels before the second cycle detected poor response to therapy with a sensitivity and specificity of 69.2% and 75%, respectively (area under the receiver operating characteristic [ROC] curve, 0.816). Early prediction of disease progression was achieved with a sensitivity and specificity of 85.7% and 92.9%, respectively, for nucleosome levels before cycle 2 (area under the ROC curve, 0.930).
The monitoring of plasma nucleosome levels during the course of first-line chemotherapy could identify patients who are likely to have insufficient response to therapy and disease progression at an early stage. This might help in individualizing treatment and could lead to better management of advanced-stage lung cancer.
近年来,抗癌药物研发领域取得了诸多进展,为提高癌症患者的生存率提供了更多选择。然而,为了改善不可手术癌症患者的治疗管理,仍需要更有效的诊断工具来早期指示治疗效果或疾病进展。
在开始化疗的第一个周期前,对 134 例晚期非小细胞肺癌患者的血浆核小体水平进行了定量检测。对接受一线化疗的 42 例患者的第二和第三个化疗周期前也进行了检测。核小体与治疗后第 3 个治疗周期后的计算机断层扫描评估的治疗反应相关联。
与无变化或进展的患者相比,缓解的患者在治疗周期 2 和 3 之前的核小体水平明显更低。在化疗过程中核小体水平升高且下降不足表明预后不良。在第二个周期前的核小体水平可检测出对治疗的不良反应,其敏感性和特异性分别为 69.2%和 75%(接受者操作特征曲线下面积,0.816)。在第二个周期前的核小体水平可以早期预测疾病进展,其敏感性和特异性分别为 85.7%和 92.9%(接受者操作特征曲线下面积,0.930)。
在一线化疗过程中监测血浆核小体水平可以识别出那些对治疗反应不足和疾病进展的患者,并能在早期进行。这可能有助于个体化治疗,并能改善晚期肺癌的治疗管理。