Maione Paolo, Rossi Antonio, Di Maio Massimo, Gridelli Cesare
Division of Medical Oncology, S.G. Moscati Hospital, Contrada Amoretta, Avellino 83100, Italy.
Lung Cancer. 2009 Oct;66(1):8-14. doi: 10.1016/j.lungcan.2009.02.022. Epub 2009 Mar 27.
Tumor-related leucocytosis is a paraneoplastic syndrome that is encountered occasionally in the clinical course of patients with non-small cell lung cancer (NSCLC). Autonomous production of hematopoietic cytokines (granulocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor) has been identified in some of the patients presenting with this syndrome. In addition to the widely accepted prognostic factors of performance status and disease stage, recently, leucocytosis has been found to be a significant negative prognostic factor for overall survival and time to progression in patients with advanced-stage NSCLC in a pooled analysis of North Central Cancer Treatment Group trials, with data from about 1000 patients. A pooled analysis of an Italian Group with data from about 1300 patients has recently shown that neutropenia during chemotherapy is associated with increased survival of patients with advanced NSCLC. Similar results on the independent prognostic value of chemotherapy-induced neutropenia, have been reported by the Hellenic Oncology Research Group in a retrospective analysis on 850 patients. The absence of chemotherapy-induced neutropenia can be interpreted as a result of chemotherapy-underdosing. However, considering the negative prognostic value of leucocytosis, another interpretation should be ruled out: a proportion of the patients who do not experience chemotherapy-induced neutropenia may be associated with a worst prognosis because they may be characterized by base-line tumor-related leucocytosis and autonomous production of hematopoietic cytokines protecting them from chemotherapy-induced neutropenia. Prospective trials are needed to assess if NSCLC-related leucocytosis and chemotherapy-induced neutropenia are two linked or independent prognostic factors for NSCLC. This paper is a review of the available retrospective evidence on the aetiology and prognostic value of tumor-related leucocytosis and on the prognostic value of chemotherapy-induced neutropenia in advanced NSCLC. Moreover we try to hypothesize a possible correlation between these two phenomena and to give suggestions on the prospective evaluation of this hypothetical correlation in the next future.
肿瘤相关性白细胞增多是一种副肿瘤综合征，在非小细胞肺癌（NSCLC）患者的临床病程中偶尔会遇到。在一些出现该综合征的患者中，已发现造血细胞因子（粒细胞集落刺激因子、粒细胞巨噬细胞集落刺激因子）的自主产生。除了广泛认可的体能状态和疾病分期等预后因素外，最近，在对约1000例患者的北中部癌症治疗组试验汇总分析中发现，白细胞增多是晚期NSCLC患者总生存期和疾病进展时间的一个显著不良预后因素。意大利研究组对约1300例患者的数据进行的汇总分析最近显示，化疗期间的中性粒细胞减少与晚期NSCLC患者生存率的提高相关。希腊肿瘤学研究组在对850例患者的回顾性分析中报告了关于化疗诱导的中性粒细胞减少的独立预后价值的类似结果。化疗诱导的中性粒细胞减少的缺乏可被解释为化疗剂量不足的结果。然而，考虑到白细胞增多的不良预后价值，另一种解释应被排除：一部分未经历化疗诱导的中性粒细胞减少的患者可能预后更差，因为他们可能具有基线肿瘤相关性白细胞增多和造血细胞因子的自主产生，从而使他们免受化疗诱导的中性粒细胞减少的影响。需要进行前瞻性试验来评估NSCLC相关性白细胞增多和化疗诱导的中性粒细胞减少是否是NSCLC的两个相关或独立的预后因素。本文是对关于肿瘤相关性白细胞增多的病因和预后价值以及化疗诱导的中性粒细胞减少在晚期NSCLC中的预后价值的现有回顾性证据的综述。此外，我们试图推测这两种现象之间可能的相关性，并对在不久的将来对这种假设相关性进行前瞻性评估提出建议。
