ALK融合基因阳性晚期肺腺癌克唑替尼耐药后治疗的效果分析#br# #br#

目的探讨间变性淋巴瘤激酶（ALK）融合基因阳性晚期肺腺癌经克唑替尼治疗失败后不同治疗方案的效果和不良反应。 方法收集本院2014年1月至2017年10月诊治的ALK融合基因阳性经克唑替尼治疗耐药的晚期肺腺癌患者65例,其中接受ALK抑制剂治疗13例,全身化疗52例（培美曲塞联合铂类23例、紫杉醇联合铂类10例、长春瑞滨联合铂类3例、吉西他滨联合铂类5例、培美曲塞单药5例和多西他赛单药6例）,2个周期后分别采用RECIST 11版与NCI CTC 40版标准评价疗效和不良反应,根据随访数据分析不同治疗方案的预后情况。 结果全组均可评价疗效,客观有效率（RR）为462％,疾病控制率（DCR）为738％。使用2代ALK抑制剂者的RR优于全身化疗者（769％ vs. 385％,P=0013）;全身化疗者中,含培美曲塞方案的RR优于不含培美曲塞方案（536％ vs.208％,P=0016）,含铂方案的DCR优于不含铂单药治疗（805％ vs.364％,P=0013）。全组中位无进展生存期（PFS）为40个月（95％CI：32～48个月）,使用2代ALK抑制剂者的中位PFS为100个月,优于全身化疗者的40个月（P=0003）。全组中位总生存期（OS）为190个月（95％CI：174～206个月）,使用2代ALK抑制剂者的中位OS为250个月,优于全身化疗者的185个月（P=0012）;EGOG评分0～1分的中位OS为195个月,优于2分的170个月（P=0004）;临床分期为ⅢB期的中位OS为265个月,优于Ⅳ期的185个月（P=0046）。 结论ALK融合基因阳性晚期肺腺癌患者克唑替尼耐药后,给予2代ALK抑制剂的治疗效果较好,EGOG评分0～1分和临床分期ⅢB期患者的生存期更长。     

Unfavorable pathological complete response rate of neoadjuvant chemotherapy epirubicin plus taxanes for locally advanced triple-negative breast cancer

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m 2 plus paclitaxel 175 mg/m 2 or docetaxel 75 mg/m 2 every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages ⅡB-ⅢC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.     

晚期肺腺癌患者奥希替尼后线治疗耐药后基因突变模式研究

目的分析外周血表皮生长因子受体(epidermal growth factor receptor,EGFR)基因T790M突变的晚期肺腺癌患者后线应用奥希替尼治疗耐药后的基因突变情况,探讨可能的耐药机制。方法晚期肺腺癌患者52例,均给予奥希替尼后线治疗,并于入院次日清晨采集外周血,提取循环肿瘤DNA,采用微滴数字PCR法检测EGFR基因T790M突变情况。对外周血检出EGFR基因T790M突变者,至病情进展时再次采集外周血,采用高通量测序进行实体瘤常见突变基因检测。结果 52例患者中36例检出外周血EGFR基因T790M突变。36例患者奥希替尼耐药后再次检测,发现10例T790M突变丢失;26例T790M突变保留,其中24例新发C797S突变;4例检出EGFR基因L718Q、L718V和L792F突变;29例检出旁路基因突变,其中MET基因突变21例(8例MET基因扩增,12例单核苷酸位点变异,1例多MET基因位点突变),12例ERBB2基因突变,7例BRAF基因突变,3例KRAS/NRAS基因突变,5例PIK3CA基因突变,1例PTEN基因突变,1例NF1基因突变,17例检出2种及以...     

三阴性乳腺癌的新辅助化疗

三阴性乳腺癌是一类侵袭性较强且具有明显异质性的乳腺癌亚型,患者的总体预后较差。多项研究显示新辅助化疗后病理完全缓解的三阴性乳腺癌患者预后较好。目前已有多种化疗药物及靶向药物用于三阴性乳腺癌新辅助化疗的临床研究,部分药物显示出较高的病理学完全缓解率和良好的应用前景。