非小细胞肺癌发生脑转移的风险因素评估与脑转移患者的靶向治疗效果研究

【作者】 常杰；

【导师】 郭惠琴； 王任直；

【作者基本信息】 北京协和医学院 ， 临床医学， 2012， 博士

【摘要】 研究目的：非小细胞肺癌(NSCLC)脑转移的发病率高达30%-50%。NSCLC患者发生脑转移的风险因素目前尚不明确,本文通过对北京协和医院2008-2011年间收治的110例NSCLC患者的资料分析,来评价NSCLC患者发生脑转移(BM)的相关风险因素以及靶向治疗对于已经发生脑转移的患者的疗效。材料与方法：我们从病案库中随机抽取了从2008年至2011年在北京协和医院诊断为NSCLC的患者的病历资料进行回顾性研究。入组标准为：随机选取；至截止时间,病例完善随访；肺癌组织类型为NSCLC;已检测EGFR与K-ras突变或有条件进行检测。最后入组病例110例,其中脑转移患者22例。危险因素变量包括年龄、性别、吸烟史、家族史、原发灶部位、病理类型、EGFR突变和K-ras突变等。按照NSCLC患者发生与没发生BM的数量与危险因素暴露与否相比较来进行2检验,并计算比值比(Odds Ratio, OR),来确定暴露因素是否为NSCLC患者发生BM的危险因素。对于已经发生脑转移的患者统计其EGFR突变、靶向治疗与生存期的关系,来明确靶向治疗的效果。结果：经过分析,年龄≤55岁的患者更易发生脑转移；性别、吸烟史、家族史、原发灶部位、有无K-ras突变与NSCLC患者发生脑转移无明显联系；肺癌病理类型为腺癌的NSCLC患者更易发生脑转移,而鳞癌患者更不易发生脑转移；有EGFR突变的患者更易发生脑转移。对于脑转移患者,靶向治疗在有EGFR突变的患者中有明显的效果。结论：对于NSCLC患者,发生脑转移的主要风险因素有年龄、病理类型、EGFR突变等。其中年龄≤55岁、病理类型为腺癌以及EGFR突变阳性为比较重要的风险因素。希望能通过对于有较多风险因素的NSCLC患者进行密切的随访与干预,降低其发生脑转移的几率,提高NSCLC患者的生存率与预后。对于已经诊断脑转移的患者,采取个体化的综合治疗,特别对于有EGFR突变的患者EGFR-TKI靶向治疗,可以获得较好的疗效。更多还原

【Abstract】 ObjectivesThe morbidity of brain metastasis (BM) of non-small cell lung cancer (NSCLC) reaches up to30%-50%. The occurring risk factors of brain metastasis of patients of NSCLC are yet undefined. This study is to evaluate risk factors of brain metastasis of patients of NSCLC through data analysis of110patients treated at Peking Union Medical College Hospital (PUMCH), and to evaluate the effect of EGFR-TKI targeted therapy in patients who have got BM already.Materials and methodsWe retrospectively randomly reviewed the medical charts of patients found to have NSCLC in PUMCH between2008to2011. The set of standard for:random selection; To deadline, cases perfect follow-up; Lung cancer types for NSCLC; Already testing EGFR and K-ras mutation or conditions for testing. At last we got110cases, in which22were diagnosed BM. Expected risk factors included age, sex, smoking history, family history, initial position of cancer, pathological type, EGFR mutations and K-ras mutations. According to whether under the action of function of each possible risk factor in patients with NSCLC, we counted the number of BM and no BM, then calculated the χ2and Odds Ratio (OR), to confirm if there was contact between expected risk factor and BM. In patients who have already got BM, we analyse the relation between EGFR mutation, targeted therapy and survival time to definite the effect of targeted therapy.ResultsAfter an analysis, patients with the age<55years old were more likely to have brain metastasis. Gender, smoking history, family history, initial position of cancer and K-ras mutations did not have obvious effects on BM. The patients with pathological type of adenocarcinoma had more risk of brain metastasis while squamous cell carcinoma had less; Patients with EGFR mutations occurred more brain metastasis.In patients who have got BM, targeted therapy have obvious effect in ones who have EGFR mutations.ConclusionFor patients with NSCLC, the main risk factors of brain metastasis happening are age, pathological type, and EGFR mutations. Age≤55years old, pathologic type being adenocarcinoma, and presence of EGFR mutations are important positive risk factors. We hope to have close follow-up and intervention for the NSCLC patients with many risk factors, to decrease the risk of brain metastases occuring, and to improve the overall survival and prognosis of patients with NSCLC. To patients having the diagnosis of brain metastases, taking individual treatment, especially for patients with EGFR mutations, EGFR-TKI targeted therapy can obtain good effect.更多还原