肺癌支气管动脉灌注化疗联合氩氦刀冷冻消融治疗临床观察

目的探讨氩氦刀冷冻消融联合支气管动脉灌注化疗的治疗效果。方法 2009年10月至2014年5月对未手术(不适合+不接受)的20例肺癌患者进行支气管动脉灌注化疗联合氩氦刀冷冻消融术。男15例,女5例。年龄40~77岁,平均62岁。全组病例均有病理活检(腺癌8例,鳞癌7例,小细胞肺癌5例),病灶直径3.0~12.0 cm,平均8.2 cm。同期,单纯支气管动脉化疗栓塞20例,男12例,女8例,年龄42~75岁,平均59.9岁,腺癌10例,腺鳞癌1例,鳞癌8例,小细胞肺癌1例。病灶直径4.0~13.0 cm,平均9.0 cm。对其并发症、无进展性生存期和生存期进行回顾性分析。结果冷冻消融手术结束时即该死亡1例,即刻气胸急诊行胸腔闭式引流1例,联合治疗组中位总生存期(PFS)为28.0个月;中位生存时间34.0个月,1年生存率91.8%,2年生存率53.0%。单纯支气管动脉灌注化疗组中位PFS为25.0个月,中位生存时间27.0个月,1年生存率87.0%,2年生存率35.5%。结论支气管动脉灌注化疗联合氩氦刀冷冻消融术对未手术的肺癌病人是安全、有效、可行的。     

氩氦冷冻消融治疗进展期肝癌的疗效及其影响因素研究

目的探讨氩氦冷冻消融治疗乙型肝炎相关性进展期肝细胞癌(HCC)的临床疗效和影响生存期的因素。方法采用临床列队对照研究190例乙型肝炎相关性进展期HCC患者,其中147例行氩氦冷冻消融治疗,43例未行局部消融和肝动脉化疗栓塞治疗。结果氩氦冷冻消融乙型肝炎相关性进展期HCC患者生存期为10.11个月,未治疗者生存期仅为4.73个月,氩氦冷冻消融治疗进展期HCC严重肝损伤发生率为5.4%,Child-Pugh分级≥B8的病例占87.5%,胆红素水平51.3μmol/L者占75%;在HBV相关性进展期HCC中,HBV DNA载量中、低水平占91%,HBeAg阴性患者占66.67%,两者与肿瘤细胞分化程度无关;肝硬化程度及肿瘤细胞分化程度是影响进展期HCC患者生存期的关键因素。结论冷冻消融治疗乙型肝炎相关性进展期HCC能显著延长患者的生存期,是影响进展期HCC生存期的独立因素;Child-Pugh分级≥B8,伴有胆红素水平51.3μmol/L的进展期HCC患者不适宜行冷冻消融;肝硬化程度及肿瘤细胞分化程度是影响进展期HCC患者生存期的关键因素。     

EGFR-TKIs联合化疗治疗晚期EGFR突变肺腺癌临床分析

目的 分析真实世界中EGFR-TKIs联合化疗治疗晚期EGFR突变肺腺癌的疗效和安全性。方法 回顾性分析2017年6月1日至2021年3月30日我院一线接受培美曲塞含铂方案联合EGFR-TKIs或培美曲塞联合EGFR-TKIs治疗晚期EGFR突变肺腺癌56例，评价临床疗效和毒性反应。结果 纳入患者的客观缓解率为：73.2%;疾病控制率为：100%;中位无进展生存期为13.50个月(95%CI:9.33～16.77);中位总生存期为：33.00个月(95%CI:23.67～42.33)。3级非血液毒性反应为：谷丙转氨酶增高为3.6%(2/56);疲劳3.6%(2/56);厌食症1.8%(1/56)。多因素分析中，ECOG PS HR:2.032(P=0.008);Ki-67 HR:1.023(P=0.011)为PFS的独立预后因素；脑转移HR:3.350(P=0.008)、Ki-67 HR:1.023(P=0.045)、二线治疗方案HR:1.687(P=0.026)为OS的独立预后因素。结论 真实世界中，培美曲塞含铂方案联合EGFR-TKIs或培美曲塞联合EGFR-TKIs治疗晚期EGF...     

氩氦刀联合肝动脉栓塞化疗与单纯氩氦刀治疗原发性肝癌比较研究

目的比较氩氦刀冷冻消融治疗联合肝动脉灌注化疗栓塞（TACE）与单纯氩氦刀治疗原发性肝癌的优劣。方法 86例原发性肝癌患者随机分为2组,A组43例行单纯氩氦刀冷冻消融治疗,B组43例行氩氦刀冷冻消融治疗联合TACE。分别在治疗前、治疗后8、15、30和50 d监测并记录各组甲胎蛋白（AFP）的动态变化。结果与A组比较,B组的AFP下降明显（P〈0.05）。结论氩氦刀冷冻消融联合TACE治疗原发性肝癌是一种微创、安全、有效的新方法,对于不适宜手术切除治疗的肝癌患者是一种有效的治疗方法。     

综合靶向消融治疗中晚期肝癌的临床研究

目的 探讨用氩氦刀冷冻 微波消融 化学消融等综合靶向消融治疗中晚期肝癌的疗效.方法 78例中晚期肝癌患者采用综合靶向消融治疗,先行肝动脉栓塞化疗,一周后行局部氩氦刀冷冻术、微波消融或化学消融术;56例单纯行动脉栓塞化疗.结果 治疗组1年生存率56.4%,对照组1年生存率36.9%;治疗组AFP平均值低于对照组,有显著性差异.结论 综合靶向消融治疗能提高中晚期肝癌患者的生存率,较单纯介入疗法治疗更为有效.     

肝动脉化疗栓塞联合氩氦刀冷冻消融治疗对不能手术的中晚期肝癌疗效的临床观察

目的观察肝动脉化疗栓塞术(TACE)联合氩氦刀冷冻消融技术治疗不能手术的中晚期肝癌患者的有效性和安全性。方法对2008年5月-2010年6月郑州大学附属洛阳中心医院收治的35例肝癌患者首先行TACE治疗2~3周,然后行氩氦刀冷冻消融治疗,1~2周后再次进行TACE治疗,治疗结束后评价近期疗效,并随访生存情况。两组间数据比较采用t检验,生存曲线采用Kaplan-Meier法进行生存分析。结果 35例患者均可评价疗效,其中完全缓解7例,部分缓解21例,稳定4例,进展3例;临床治疗有效率为80.00%,疾病控制率为91.43%;2、3年生存率分别为45.6%、39.4%。35例患者治疗前甲胎蛋白(AFP)为(837.6±216.7)μg/L,治疗后AFP为(206.2±48.6)μg/L,差异有统计学意义(t=2.673,P0.05)。结论 TACE联合氩氦刀冷冻消融是治疗不能手术的中晚期肝癌患者的可靠方法,具有创伤小、恢复快、并发症少等特点。     

血清癌胚抗原联合神经元特异性烯醇化酶可预测晚期肺腺癌患者酪氨酸激酶抑制剂治疗的疗效

目的:探讨血清癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)对晚期肺腺癌患者表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)疗效的评估价值。方法:回顾性分析2013年1月至2016年4月四川省遂宁市中心医院采取EGFR-TKIs治疗的EGFR突变阳性ⅢB期、Ⅳ期肺腺癌患者103例的临床资料,依据治疗后24个月的生存情况将患者分为存活组(36例)和死亡组(67例)。比较2组患者治疗前、后的血清CEA、NSE水平及其降低值;采用Logistic多因素分析血清CEA、NSE降低值对晚期肺腺癌患者EGFR-TKIs疗效的预测。结果:随访24个月,存活组治疗前、后的血清CEA、NSE降低值大于死亡组(P 0. 05); Logistic多因素分析显示,治疗前ECOG体力状态评分升高、TNM分期增高、组织学低分化是晚期肺腺癌患者EGFR-TKIs治疗不良预后的独立危险因素(P均0. 05); ROC曲线分析显示,血清CEA降低值联合NSE降低值预测晚期肺腺癌患者24个月生存的灵敏度为91. 62%,特异度为78. 77%,ROC曲线下面积AUC值为0. 916。结论:血清CEA和NSE可联合预测晚期肺腺癌患者EGFR-TKIs疗效,其水平降低越显著,越有利于患者生存。     

支气管动脉化疗+栓塞与支气管动脉化疗联合氩等离子体治疗晚期中央型肺癌的疗效比较

目的探讨应用支气管动脉化疗联合氩等离子体治疗晚期中央型肺癌的近期疗效。方法分析比较我院45例晚期中央型肺癌分别行支气管动脉化疗+栓塞与支气管动脉化疗联合氩等离子体治疗疗效差别。结果支气管动脉化疗联合氩等离子体治疗晚期中央型肺癌组实体瘤缓解率(87.5%)及气道狭窄再通改善率(91.7%)明显优于支气管动脉化疗+栓塞组的57.1%及52.4%,且近期生存质量好。结论应用支气管动脉化疗联合氩等离子体治疗晚期中央型肺癌近期疗效明显优于支气管动脉化疗+栓塞治疗组,且能提高患者生活质量。     

培美曲塞治疗老年晚期肺腺癌的临床观察

目的观察培美曲塞单药与联合卡铂治疗老年晚期肺腺癌的疗效及不良反应。方法 56例晚期肺腺癌患者,培美曲塞单药治疗27例,培美曲塞联合卡铂治疗29例,评价疗效及不良反应。结果 56例中无CR病例。单药组PR 2例,SD 14例,中位PFS为3.5个月,中位OS为9.1个月;联合组PR 3例,SD 16例,中位PFS为3.9个月,中位OS为9.8个月。两组比较,DCR、中位PFS、中位OS差异均无统计学意义(P>0.05)。不良反应主要为骨髓抑制、胃肠道反应及皮疹。结论培美曲塞二线治疗晚期肺腺癌疗效确切,患者耐受性较好。     

PIK3CA突变对EGFR-TKIs治疗EGFR19/21突变肺腺癌疗效的影响

目的 探讨PIK3CA突变对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗EGFR19/21突变肺腺癌疗效的影响。方法 选择肺腺癌患者80例，其中PIK3CA与EGFR19/21共突变20例（共突变组）、EGFR19/21单突变60例（单突变组），均予第一代EGFR-TKIs（埃克替尼或吉非替尼）口服治疗。口服治疗28天评价疗效，之后每8～12周评价1次，记录最佳疗效，计算客观缓解率（ORR）、疾病控制率（DCR）。随访截至2022年12月31日或患者死亡，统计无进展生存期（PFS）、总体生存期（OS）。比较两组近期疗效（ORR、DCR）和远期疗效（PFS、OS）。采用单变量和多变量Cox回归模型分析PIK3CA与EGFR19/21共突变肺腺癌患者远期疗效的影响因素。结果 共突变组与单突变组临床资料比较差异均无统计学意义（P均>0.05）。共突变组ORR、DCR均低于单突变组，中位PFS、中位OS亦均低于单突变组（P均<0.05）。单变量Cox回归分析显示，年龄、ECOG评分可能与PIK3CA与EGFR19/21共突变肺腺癌患者PFS有关（P均<0.10）...     

EGFR基因21外显子L858R突变肺腺癌患者化疗和靶向治疗疗效的回顾性分析

目的探讨EGFR基因21外显子L858R突变肺腺癌患者使用化疗和EGFR-TKI靶向治疗疗效的差异。方法回顾性分析,收集第三军医大学新桥医院2010年1月至2015年12月间EGFR基因检测为21外显子L858R突变的病例资料完整的ⅢB/Ⅳ期一线接受化疗或EGFR酪氨酸激酶抑制剂(EGFR-TKI)靶向治疗的肺腺癌患者作为研究对象,将患者根据一线治疗方式分为化疗组和靶向治疗组,对两组患者近期疗效(客观缓解率ORR、疾病控制率DCR)及生存期(无进展生存期PFS、总生存期OS)进行回顾性研究。结果 1共收集符合纳入标准的EGFR基因21外显子L858R突变的肺腺癌患者68例,其中化疗组患者40例(58.8%),靶向治疗组患者28例(41.2%),两组患者在性别、年龄、吸烟史、PS评分和临床分期等临床资料基线水平一致(P0.05);2化疗和靶向治疗组ORR分别为45.0%和17.9%(P=0.020);DCR分别为95.0%和71.4%(P=0.012),PFS分别为9.901个月和6.746个月(P=0.045);OS分别为21.738个月和23.611个月(P=0.378)。结论与靶向治疗相比,EGFR基因21外显子L858R突变肺腺癌患者化疗治疗在近期疗效及PFS上较有优势,OS未见明显获益。     

Solid predominant histology predicts EGFR tyrosine kinase inhibitor response in patients with EGFR mutation-positive lung adenocarcinoma

Background

The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) differs in patients with lung adenocarcinoma harboring EGFR-activating mutations. Although lung adenocarcinoma with EGFR-activating mutations has heterogeneous morphologic features, the predictive role of histologic subtype of lung adenocarcinoma with regard to the effectiveness of EGFR-TKIs in patients with EGFR-activating mutations has not been well defined.

Methods

Among 134 postoperative recurrence patients with lung adenocarcinoma harboring EGFR-activating mutation (L858R or exon 19 deletion) treated with EGFR-TKIs, we retrospectively analyzed 61 patients treated with EGFR-TKIs as first-line chemotherapy. All the tumors were classified according to the new histologic classification proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) into the following subtypes: lepidic, papillary, acinar, micropapillary, or solid predominant subtype. We evaluated the correlation between the histologic subtype and the clinical efficacy of EGFR-TKIs.

Results

In overall response rate, adenocarcinoma with solid predominant subtype is significantly worse than with non-solid predominant subtype (61 vs. 88 %, P = 0.03). The median progression-free survival (PFS) and overall survival after EGFR-TKI treatment were significantly shorter for the patients with solid predominant subtype than for those with non-solid predominant subtype (median PFS of 7.7 vs. 13.5 months, P = 0.002, and median OS of 21.5 vs. 31.0 months, P = 0.028).

Conclusions

This study indicated that among patients with lung adenocarcinoma harboring activating EGFR mutations treated with EGFR-TKIs, solid predominant subtype according to IASLC/ATS/ERS classification is a response predictor for EGFR-TKI.     

晚期肺腺癌患者维持治疗中EGFR-TKI联合放疗的回顾性分析

目的探讨EGFR突变阳性的晚期肺腺癌患者经EGFR-TKI诱导治疗后,以EGFR-TKI联合胸部放疗作为维持治疗的疗效和安全性。 方法收集陆军军医大学西南医院2012年1月至2019年7月收治的EGFR突变阳性、接受一线EGFR-TKI治疗并达到疾病稳定的晚期肺腺癌患者的临床资料,EGFR-TKI诱导治疗达疾病稳定后联合胸部放疗维持为联合治疗组,单药TKI维持为单药治疗组。对两组患者的无进展生存期(PFS)、缓解持续时间(DOR)、客观缓解率(ORR)、疾病控制率(DCR)和不良反应进行回顾性分析。 结果共收集符合标准的患者178例,其中联合治疗组23例,单药治疗组155例,经过倾向性得分匹配(PSM)1︰1匹配后,配对成功21对。两组在临床资料基线水平一致(P>0.05),两组的中位PFS分别为19.8个月和12.3个月(P＝0.000),中位DOR分别为16.5个月和9.8个月(P＝0.002),ORR分别为85.7%和76.2%(P＝0.687),DCR都是100%,3级及以上不良反应分别为5例(23.8%)、4例(19.0%)。两组共同的不良反应相差不大,最常见的为皮疹,分别为9例(42.8%)和10例(47.6%)。联合治疗组出现放射性肺炎11例(52.4%),其中1级10例,2级1例。 结论一线EGFR-TKI诱导治疗后,EGFR-TKI联合胸部放疗维持治疗比EGFR-TKI单药维持治疗有更好的PFS获益,并且联合组安全性可耐受。     

EGFR-TKI治疗非小细胞肺癌EGFR突变阳性脑转移的临床对比观察

目的探讨EFGR-TKI(厄洛替尼与吉非替尼)治疗非小细胞肺癌(NSCLC)EGFR突变阳性脑转移患者的临床疗效。方法回顾收集分析我科73例EGFR突变阳性的肺腺癌脑转移患者的临床病历资料,患者均口服厄洛替尼150mg/d(39例)或吉非替尼250 mg/d(34例),服药直至患者颅内外病情进展、死亡、出现不可耐受的副反应或不能控制的新发病灶。结果厄洛替尼组与吉非替尼组颅内病变的有效率(RR)和疾病控制率(DCR)分别为51.3%,94.9%和53.0%,94.1%(P=0.861),两组颅外病变的有效率和疾病控制率分别为59.0%,97.4%和50.0%,97.1%(P=0.793),两组患者的中位无进展生存期(PFS)和总生存期(OS)分别为11.3个月和15.1个月vs12.1个月和16.4个月(P=0.913,P=0.641)。两种药物的副反应均较小,患者都可以耐受。结论 EGFR-TKI对EGFR突变阳性的NSCLC脑转移均具有较好地疗效,可作为EGFR突变阳性脑转移患者的一线或二线治疗,药物副反应较小,两种药物对患者的预后无明显差异。     

Erlotinib as a salvage treatment after gefitinib failure for advanced non-small-cell lung cancer patients with brain metastasis: A successful case report and review

Rationale:The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib.Patient concerns:We described a 55-year-old man with good performance status (PS).Diagnoses:He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018.Interventions:He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib.Outcomes:It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable.Lessions:This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.     

Transformation of NSCLC to SCLC after 1st- and 3rd-generation EGFR-TKI resistance and response to EP regimen and erlotinib: 2 CARE-compliant case reports

Rationale:Genotypic and histological evolution of non-small-cell lung cancer (NSCLC) into small-cell lung cancer (SCLC) has been described as a mechanism of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy. However, the number of clinical cases is rare.Patient concerns:Two lung adenocarcinoma patients with EGFR mutations who recurred after radical resection transformed into SCLC under treatment with the sequential first- and third-generation EGFR-TKIs.Diagnosis:The 2 cases were both confirmed as SCLC by pathological rebiopsy after EGFR-TKIs resistance.Interventions:Case 1 was treated with etoposide plus cisplatin (EP) regimen and erlotinib, while case 2 was treated with erlotinib and EP followed by oral etoposide.Outcomes:Case 1 treated with EP only achieved 3-month progression-free survival (PFS), which is the first case that reported T790 M/C797S cis-mutation for osimertinib resistance before the SCLC transformation. However, case 2 treated with erlotinib and EP followed by oral etoposide, PFS lasted for 8 months.Lessons:The cases highlighted the importance of rebiopsy that identified pathologically SCLC transformation after EGFR-TKI resistance, and suggested the treatment of erlotinib plus EP followed by etoposide, which could provide a reference for such phenotype.     

Gender-Based Impact of Epidermal Growth Factor Receptor Mutation in Patients With Nonsmall Cell Lung Cancer and Previous Tuberculosis

The association between tuberculosis (TB) and lung cancer is well known. However, carcinogenesis of TB and its connection with epidermal growth factor receptor (EGFR) mutation remains unclear. This study aimed to determine this connection to see if TB can affect the outcome of patients with lung cancer.This is a retrospective cohort study of patients with lung cancer receiving EGFR-tyrosine kinase inhibitors (TKIs) between 1996 and 2010 using the National Health Insurance Research Database of Taiwan. Because therapeutic response was required to apply EGFR-TKIs for >90 days, only patients with a follow-up of >120 days were studied and a responder was defined as intake of EGFR-TKIs >90 days. Predictors of EGFR-TKI response and survival were identified using logistic and Cox regression analyses, respectively.There were 8265 patients analyzed, including 6073 (73.5%) EGFR-TKI responder and 2192 (26.5%) nonresponder. A history of TB was found in 1.2% and 1.8% of the 2 groups, respectively. Comparing to male with pulmonary TB history, female with or without pulmonary TB history and male without pulmonary TB history all had a better EGFR-TKI response and 1-year progression-free survival (PFS). Gender and TB history were not independent prognostic factors of 2-year overall survival. The findings were similar in the subpopulation without chronic obstructive pulmonary disease, malignancies other than lung cancer, and low-income status.TB has a gender-dependent impact, with better EGFR-TKI response and 1-year PFS in female patients with lung cancer. The carcinogenesis and inflammation of TB may be different between genders.     

The predictive and prognostic effects of PD-L1 expression on TKI treatment and survival of EGFR-mutant NSCLC: A meta-analysis

Whether programmed death-ligand 1 (PD-L1) expression could predict the outcome of tyrosine kinase inhibitor (TKI) treatment and prognosis of epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) is remaining controversial.Potential studies were search from PubMed, Embase, and Web of Science databases. Pooled odds ratio of objective response rate was used to describe the relationship between PD-L1 expression and primary resistance to EGFR-TKIs. Pooled hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) were included to assess the effects of PD-L1 status on the outcome of EGFR-TKI treatment and survival of EGFR-mutant NSCLCs.Eighteen eligible studies (1986 EGFR-mutant NSCLCs) were included in this meta-analysis. Positive PD-L1 expression correlated with lower objective response rate of EGFR-TKI treatment (odds ratio [95% confidence interval {CI}] = 0.52 [0.28–0.98], P = .043), while PFS (adjusted HR [95% CI] = 1.49 [0.96–1.89], P = .332) and OS (HR [95% CI] = 1.24 [0.70–2.20], P = .456) of EGFR-TKI treatment did not correlated with PD-L1 status. Furthermore, PD-L1 expression was not a predictive biomarker for the OS (HR [95% CI] = 1.43 [0.98–2.08], P = .062) in overall EGFR-mutant cohort.Positive PD-L1 expression indicated a higher incidence of primary resistance, but did not correlate with the PFS or OS of EGFR-TKI therapy. In addition, PD-L1 expression was unlikely a predictive biomarker for prognosis of EGFR-mutant NSCLCs.     

Factors that predict progression-free survival in Chinese lung adenocarcinoma patients treated with epidermal growth factor receptor tyrosine kinase inhibitors

Background

Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown efficacy in patients with advanced lung cancers, survival predictors with these drugs have not been extensively investigated. This study was performed to explore factors that may predict progression-free survival (PFS) in Chinese lung adenocarcinoma patients treated with EGFR-TKIs.

Methods

We retrospectively collected clinicopathologic data on 208 patients who received either gefitinib, erlotinib or icotinib, including the patients’ EGFR mutation status and levels of six serum tumor markers [carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCC), cytokeratin-19 fragments (CYFRA21-1) and lactate dehydrogenase (LDH)]. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with PFS.

Results

At the study cutoff date, 189 (90.9%) of the patients met the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria for progressive disease (PD), while 19 (9.1%) had stable disease (SD). The median PFS of the 208 patients was 12.4 months (95% CI, 11.0–13.8 months). In the multivariate analysis using a Cox proportional hazard model, a non-smoking history [hazard ratio (HR) =2.460; 95% CI, 1.484–4.079; P<0.001], first-line treatment (HR =1.500; 95% CI, 1.062–2.119; P=0.021), and a high pretreatment serum level of CEA (HR =1.424; 95% CI 1.026–1.977; P=0.035) were found to be significant predictors of a longer PFS.

Conclusions

In Chinese lung adenocarcinoma patients treated with EGFR-TKIs, a non-smoking history, first-line EGFR-TKIs treatment and a high serum level of CEA were independent predictors of a longer PFS along with an EGFR-activating mutation.     

非小细胞肺癌表皮生长因子受体突变的检测与分子靶向治疗

目的探讨非小细胞肺癌患者表皮生长因子受体(EGFR)基因突变率和突变类型,分析其临床特征,并观察EGFR突变与表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗疗效的相关性。方法收集203例非小细胞肺癌患者外科手术、淋巴结活检、经皮肺穿刺活检、气管镜活检和胸腔积液沉渣石蜡标本,应用ADx-ARMS法进行EGFR基因突变检测,分析基因的突变率及其与临床特征的关系;观察非小细胞肺癌(NSCLC)接受EGFR-TKIs治疗的非小细胞肺癌患者的疗效。应用SPSS23.0软件进行统计学分析,计数资料比较采用χ2检验,采用Kaplan-Meier法计算患者的PFS,采用Log-Rank检验分析各种因素对生存期的影响。结果 203例NSCLC患者,男性116例,女性87例,年龄为25~82岁。吸烟指数≥400支/者61例,小于400支/年和不吸烟者142例,腺癌152例,鳞癌21例,腺鳞癌14例,其他NSCLC16例。203例NSCLC患者EGFR总突变率为51.2%(104/203),包括19外显子缺失突变51例(49.0%),21外显子L858R突变44例(42.3%),19del及L858R总突变率占所有突变的96.1%,18外显子G719X点突变3例(2.9%),19del+L858R双突变3例(2.9%),1例20ins,2例T790M突变分别为1例19del+T790M和1例L858R+T790M。EGFR基因阳性突变率女性组高于男性组(66.7%vs.36.2%);非吸烟组高于吸烟组(63.4%vs.16.4%);腺癌组高于鳞癌组(53.3%vs.33.3%),P0.05。而EGFR基因突变状况与标本类型如手术、淋巴结活检、肺穿刺活检、气管镜活检和胸腔积液沉渣标本间无统计学差异,P=0.418。101例接受TKI治疗的NSCLC患者客观缓解率(ORR)为61.4%,疾病控制率(DCR)为71.3%,中位疾病无进展生存期(PFS)为10个月。其中EGFR突变阳性患者接受EGFR-TKIs治疗的ORR及DCR均要显著高于EGFR突变阴性及EGFR突变状态未明确人群(88.6%vs.16.7%vs.43.1%,P=0.000;95.5%vs.16.7%vs.56.9%,P=0.000)。EGFR突变阳性患者接受EGFR-TKIs治疗的中位PFS较EGFR突变阴性及EGFR突变状态未明确患者延长,有统计学差异(P=0.001)。进一步分析EGFR突变阳性19del组NSCLC患者ORR、DCR均高于L858R组(91.2%vs.85%,P=0.646;100%vs.90%,P=0.201);19del组NSCLC患者TKI治疗后中位PFS 14.5个月较L858R组10个月长,有统计学差异(P=0.010)。结论非小细胞肺癌患者EGFR突变高,以女性、不吸烟、腺癌为优势人群,EGFR敏感突变阳性者对EGFR-TKI疗效好,EGFR突变中19del者较L858R疗效更佳,基因检测结果可以较好地预测分子靶向药物的疗效,降低肿瘤进展的风险。