The correlation between chemotherapeutic efficacy and breast cancer susceptibility gene 1 and class Ⅲ β-tubulin protein expression in non-small cell lung cancer patients

Objective To investigate the predictive value of breast cancer susceptibility gene 1 (BRCA1) and class Ⅲβ-tubulin protein expression in tumor tissue for the efficacy of taxol and cisplatin combined chemotherapy (TP) in stage Ⅲβ/Ⅳ non-small cell lung cancer(NSCLC) patients. Methods A total of 92 stage Ⅲβ/Ⅳ NSCLC patients were recruited with 87 patients evaluated. Bronchoscopy or lung puncture tumor biopsy samples were obtained with BRCA1 and class Ⅲβ-tubulin protein expression examined immunohistochemically before chemotherapy. The patients were randomly assigned to be received 4 to 6 cycles of TP chemotherapy regiments and followed up until death or lost. Response rate (RR) , overall survival (OS) and time to tumor progression (TTP) were assessed. Results Among the 87 evaluated patients, the positive expression rates of BRCA1 and class Ⅲβ-tubulin were 57. 5% (50/87) and 48. 3%(42/87) respectively. There was no significant difference in clinical characteristics among patients with different positive expression rate. According to different expression of BRCA1 and class Ⅲβ-tubulin, the patients were divided into four groups: group A (low expression of both BRCA1 and class 1 p-tubulin) ,group B (high expression of both BRCA1 and class Ⅲβ-tubulin) , group C (high expression of only BRCA1) and group D (high expression of only class Ⅲβ-tubulin). The RR was higher in group A than other three groups (60. 7% , 34. 8% , 9/19 and 6/17 respectively). The OS and TTP were longer in group A than other three groups [OS: (539. 4 ± 17. 6) days, (267. 2 ± 20. 5) days, (325. 6 ± 24. 1) days and (283.7±26.2) days respectively ; TTP: (256. 9 ± 28. 4) days, (143.8±17.6) days, (179. 3 ± 19. 8)days and (152. 6 ±23. 5) days respectively]. There were no significant differences among the other three groups. Conclusions The expression level of BRCA1 and class Ⅲβ-tubulin in tumor tissue is probably a predictor for the efficacy of TP chemotherapy in NSCLC patients. TP chemotherapy is more suitable for the NSCLC patients with lower expression of both BRCA1 and class Ⅲβ-tubulin. Our study may provide a new sight for tailored chemotherapy in NSCLC patients.     

The correlation between chemotherapeutic efficacy and breast cancer susceptibility gene 1 and class Ⅲ β-tubulin protein expression in non-small cell lung cancer patients

Objective To investigate the predictive value of breast cancer susceptibility gene 1 (BRCA1) and class Ⅲβ-tubulin protein expression in tumor tissue for the efficacy of taxol and cisplatin combined chemotherapy (TP) in stage Ⅲβ/Ⅳ non-small cell lung cancer(NSCLC) patients. Methods A total of 92 stage Ⅲβ/Ⅳ NSCLC patients were recruited with 87 patients evaluated. Bronchoscopy or lung puncture tumor biopsy samples were obtained with BRCA1 and class Ⅲβ-tubulin protein expression examined immunohistochemically before chemotherapy. The patients were randomly assigned to be received 4 to 6 cycles of TP chemotherapy regiments and followed up until death or lost. Response rate (RR) , overall survival (OS) and time to tumor progression (TTP) were assessed. Results Among the 87 evaluated patients, the positive expression rates of BRCA1 and class Ⅲβ-tubulin were 57. 5% (50/87) and 48. 3%(42/87) respectively. There was no significant difference in clinical characteristics among patients with different positive expression rate. According to different expression of BRCA1 and class Ⅲβ-tubulin, the patients were divided into four groups: group A (low expression of both BRCA1 and class 1 p-tubulin) ,group B (high expression of both BRCA1 and class Ⅲβ-tubulin) , group C (high expression of only BRCA1) and group D (high expression of only class Ⅲβ-tubulin). The RR was higher in group A than other three groups (60. 7% , 34. 8% , 9/19 and 6/17 respectively). The OS and TTP were longer in group A than other three groups [OS: (539. 4 ± 17. 6) days, (267. 2 ± 20. 5) days, (325. 6 ± 24. 1) days and (283.7±26.2) days respectively ; TTP: (256. 9 ± 28. 4) days, (143.8±17.6) days, (179. 3 ± 19. 8)days and (152. 6 ±23. 5) days respectively]. There were no significant differences among the other three groups. Conclusions The expression level of BRCA1 and class Ⅲβ-tubulin in tumor tissue is probably a predictor for the efficacy of TP chemotherapy in NSCLC patients. TP chemotherapy is more suitable for the NSCLC patients with lower expression of both BRCA1 and class Ⅲβ-tubulin. Our study may provide a new sight for tailored chemotherapy in NSCLC patients.     

非小细胞肺癌患者肿瘤组织乳腺癌易感基因1和β微管蛋白Ⅲ表达及其与化疗疗效的关系

目的 观察肿瘤组织乳腺癌易感基因1(BRCA1)、β微管蛋白Ⅲ表达与ⅢB和(或)Ⅳ期非小细胞肺癌(NSCLC)采用紫杉醇联合顺铂(TP)方案化疗疗效的相关性.方法 入选初治、NSCLC临床TNM分期为ⅢB和(或)Ⅳ期、体能状态(PS)评分0～2分、预计生存期≥3个月的患者入选本研究.入选者均进行TP方案化疗,每3周重复,每2个周期评价1次疗效,共4～6个周期,无效者更换二线化疗方案.免疫组化检测肿瘤组织中BRCA1、β微管蛋白Ⅲ表达.根据BRCA1、β微管蛋白Ⅲ表达高低分为A组(BRCA1、β微管蛋白Ⅲ低表达)、B组(BRCA1、β微管蛋白Ⅲ高表达)、C组(BRCA1高表达,β微管蛋白Ⅲ低表达),D组(BRCA1低表达,B微管蛋白Ⅲ高表达).评价疗效指标:客观反应率(RR)、总生存时间(OS)、至肿瘤进展时间(TTP).结果 (1)人组87例ⅢB/Ⅳ期NSCLC患者,BRCA1、β微管蛋白Ⅲ表达阳性率分别为57.5%(50/87)、48.3%(42/87),BRCA1、β微管蛋白Ⅲ不同表达的NSCLC患者间临床特征比较差异无统计学意义.(2)87例患者中A组28例,B组23例,C组19例,D组17例.化疗前4组患者间的临床特征比较差异无统计学意义.4组患者RR分别为60.7%、34.8%、9/19、6/17;OS分别为(539.4±17.6)d、(267.2±20.5)d、(325.6±24.1)d、(283.7±26.2)d;TTP分别为(256.9±28.4)d、(143.8±17.6)d、(179.3±19.8)d、(152.6±23.5)d.方差分析显示,A组的RR、OS、TTP均优于其他3组,差异有统计学意义(P值分别为0.039、0.000和0.000).结论 BRCA1、β微管蛋白Ⅲ可作为TP方案疗效的预测分子;仅BRCA1、β微管蛋白Ⅲ低表达的NSCLC患者,可能是TP化疗方案的优势人群.

Abstract：

Objective To investigate the predictive value of breast cancer susceptibility gene 1 (BRCA1) and class Ⅲβ-tubulin protein expression in tumor tissue for the efficacy of taxol and cisplatin combined chemotherapy (TP) in stage Ⅲβ/Ⅳ non-small cell lung cancer(NSCLC) patients. Methods A total of 92 stage Ⅲβ/Ⅳ NSCLC patients were recruited with 87 patients evaluated. Bronchoscopy or lung puncture tumor biopsy samples were obtained with BRCA1 and class Ⅲβ-tubulin protein expression examined immunohistochemically before chemotherapy. The patients were randomly assigned to be received 4 to 6 cycles of TP chemotherapy regiments and followed up until death or lost. Response rate (RR) , overall survival (OS) and time to tumor progression (TTP) were assessed. Results Among the 87 evaluated patients, the positive expression rates of BRCA1 and class Ⅲβ-tubulin were 57. 5% (50/87) and 48. 3%(42/87) respectively. There was no significant difference in clinical characteristics among patients with different positive expression rate. According to different expression of BRCA1 and class Ⅲβ-tubulin, the patients were divided into four groups: group A (low expression of both BRCA1 and class 1 p-tubulin) ,group B (high expression of both BRCA1 and class Ⅲβ-tubulin) , group C (high expression of only BRCA1) and group D (high expression of only class Ⅲβ-tubulin). The RR was higher in group A than other three groups (60. 7% , 34. 8% , 9/19 and 6/17 respectively). The OS and TTP were longer in group A than other three groups [OS: (539. 4 ± 17. 6) days, (267. 2 ± 20. 5) days, (325. 6 ± 24. 1) days and (283.7±26.2) days respectively ; TTP: (256. 9 ± 28. 4) days, (143.8±17.6) days, (179. 3 ± 19. 8)days and (152. 6 ±23. 5) days respectively]. There were no significant differences among the other three groups. Conclusions The expression level of BRCA1 and class Ⅲβ-tubulin in tumor tissue is probably a predictor for the efficacy of TP chemotherapy in NSCLC patients. TP chemotherapy is more suitable for the NSCLC patients with lower expression of both BRCA1 and class Ⅲβ-tubulin. Our study may provide a new sight for tailored chemotherapy in NSCLC patients.     

真实世界老年小细胞肺癌患者一线免疫联合化疗疗效与不良反应观察

目的探讨真实世界中老年小细胞肺癌(SCLC)患者一线免疫联合化疗疗效和不良反应。方法回顾性分析2013年1月至2023年6月就诊于北京医院经穿刺/气管镜活检或手术病理明确诊断SCLC并接受一线内科治疗的广泛期老年患者(≥65岁)148例, 其中化疗组103例、免疫联合化疗组(联合组)45例。按年龄分为≥75岁组和<75岁组, 比较不同年龄组、一线不同治疗方式的疗效和免疫相关不良反应情况。评价程序性死亡配体1(PD-L1)表达和肿瘤突变负荷(TMB)表达情况及与生存的关系。采用实体瘤疗效评价标准(RECIST1.1)评价近期疗效, 常见不良反应分级评价标准(CTCAE 4.03)评价免疫相关不良反应。Kaplan-Meier法进行生存曲线分析, 并进行Log-rank检验。Cox风险比例回归模型分析影响预后的因素。结果老年SCLC患者一线联合组总有效率(ORR)79.1%(34/43), 高于化疗组63.2%(60/95), 但差异未达到统计学意义(χ2=3.451, P=0.063)。≥75岁组患者联合组ORR显著高于化疗组, 分别为87.5%(7/8)比48.6%(17/35)...     

术前免疫检查点抑制剂联合化疗治疗可切除Ⅲ期非小细胞肺癌的疗效及患者近期预后的影响因素分析

目的 分析免疫检查点抑制剂(ICI)联合化疗治疗可切除Ⅲ期非小细胞肺癌(NSCLC)的疗效,并探讨患者近期预后的影响因素。方法 回顾性收集2019年1月至2021年5月武汉大学人民医院收治的可切除Ⅲ期NSCLC患者45例为研究对象。患者均经ICI联合含铂双药化疗方案治疗后进行手术治疗。记录患者临床疗效、毒副作用发生情况、手术情况、术后住院时间、术后并发症发生情况、随访情况。以主要病理缓解(MPR)为可切除Ⅲ期NSCLC患者近期预后评定指标,并根据其将患者分为MPR组与非MPR组;采用多因素Logistic回归分析探讨可切除Ⅲ期NSCLC患者近期预后影响因素。结果 45例患者完成ICI联合化疗1～4个周期。完全缓解(CR)4例,部分缓解(PR)23例,病情稳定(SD)14例,疾病进展(PD)4例,客观缓解率(ORR)为60.0%,疾病控制率(DCR)为91.1%。ICI联合化疗过程中出现不同程度的毒副作用,其中出现反应性皮肤毛细血管增生症/皮疹最多,达31例(68.9%)。完成手术治疗40例,手术切除率为88.9%。术后病理结果显示达到MPR 22例(55.0%);MPR组与非MPR组美...