Abstract:

Objective　To explore the efficacy and safety of Tislelizumab combined with albumin-paclitaxel and cisplatin in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC) brain metastases. Methods　A total of 122 elderly patients with advanced NSCLC brain metastases admitted to Ankang People's Hospital from January 2018 to July 2023 were selected as the study objects. The patients were divided into an observation group (64 cases) and a control group (58 cases) according to the treatment methods. In the observation group, there were 35 males and 29 females, aged 60-85 (70.97±4.91) years, pathological types: 33 cases of squamous cell carcinoma and 31 cases of adenocarcinoma, differentiation degree: 26 poorly differentiated cases, 24 moderately differentiated cases, and 14 highly differentiated cases, pathological stage: 22 cases of stage Ⅲb and 42 cases of stage Ⅳ. In the control group, there were 32 males and 26 females, aged 62-83 (72.71±4.86) years, pathological types: 31 cases of squamous cell carcinoma and 27 cases of adenocarcinoma; differentiation degree: 23 poorly differentiated cases, 25 moderately differentiated cases, and 10 highly differentiated cases, pathological stage: 19 cases of stage Ⅲb and 39 cases of stage Ⅳ. The control group was treated with albumin-paclitaxel combined with cisplatin, and the observation group was treated with Tislelizumab on the basis of the control group. With 21 days was 1 treatment cycle, both groups were treated for 4 consecutive cycles. The clinical efficacy (objective response rate and disease control rate), tumor markers [carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and soluble fragment of cytokeratin 19 (CYFRA21-1)] and immune markers (CD3⁺, CD4⁺, and CD4⁺/CD8⁺) before and after treatment, incidence of adverse reactions during treatment, and 12-month follow-up survival prognosis [progression-free survival (PFS) and overall survival (OS)] were compared between the two groups. Independent sample t test, paired t test, χ² test, Fisher exact probability method, and Log-rank test were used for statistical analysis. Results　The objective remission rate and disease control rate of the observation group were higher than those of the control group [56.25% (36/64) vs. 37.93% (22/58), 85.94% (55/64) vs. 70.69% (41/58)] (both P<0.05). After treatment, serum CEA, SCC, and CYFRA21-1 levels in the observation group were lower than those in the control group [(14.92±3.51) μg/L vs. (17.05±4.42) μg/L, (27.64±5.94) μg/L vs. (30.02±6.67) μg/L, (7.51±2.03) μg/L vs. (8.64±2.15) μg/L] (all P<0.05); the serum levels of CD3⁺, CD4⁺, and CD4⁺/CD8⁺ in the observation group were higher than those in the control group [(52.09±5.53)% vs. (39.97±5.28)%, (48.71±6.35)% vs. (36.18±5.09)%, 1.84±0.31 vs. 1.12±0.35] (all P<0.05). During treatment, there was no statistically significant difference in the incidences of adverse reactions (fever, hypothyroidism, pruritus, decrease of white blood cell count, and increase of aminotransferase) between the two groups (all P>0.05). At the end of follow-up, 2 cases were lost in the observation group and 1 case in the control group, with an effective follow-up rate of 97.54%(119/122). The median PFS of the observation group and the control group were 9 months and 6 months, respectively. The median OS of the control group was 11 months, and the median OS of the observation group was not reached. After 12 months of follow-up, the overall survival rate of the observation group was higher than that of the control group [69.35% (43/62) vs. 47.37% (27/57)] (P<0.05). There were statistically significant differences in the PFS and OS between the two groups (both P<0.05). Conclusion　Tislelizumab combined with albumin-paclitaxel and cisplatin in the treatment of elderly patients with advanced NSCLC brain metastases can inhibit the expressions of tumor markers, regulate the immune function, improve the efficacy, and have good safety.

Key words:

Non small cell lung cancer, Brain metastases, Old age, Albumin-paclitaxel, Cisplatin, Tislelizumab

摘要：

目的　探讨替雷利珠单抗联合白蛋白紫杉醇和顺铂治疗老年晚期非小细胞肺癌（NSCLC）脑转移患者的效果及安全性。方法　选取2018年1月至2023年7月安康市人民医院收治的122例老年晚期NSCLC脑转移患者作为研究对象。根据治疗方法，将患者分为观察组（64例）和对照组（58例）。观察组男35例，女29例；年龄60～85（70.97±4.91）岁；病理类型：鳞癌33例，腺癌31例；分化程度：低分化26例，中分化24例，高分化14例；病理分期：Ⅲb期22例，Ⅳ期42例。对照组男32例，女26例；年龄62～83（72.71±4.86）岁；病理类型：鳞癌31例，腺癌27例；分化程度：低分化23例，中分化25例，高分化10例；病理分期：Ⅲb期19例，Ⅳ期39例。对照组采用白蛋白紫杉醇联合顺铂治疗，观察组在对照组基础上联合替雷利珠单抗治疗。21 d为1个治疗周期，两组均连续治疗4个周期。比较两组临床疗效（客观缓解率、疾病控制率），治疗前后肿瘤标志物［癌胚抗原（CEA）、鳞状上皮细胞癌抗原（SCC）、细胞角蛋白19可溶性片段（CYFRA21-1）］、免疫指标（CD3⁺、CD4⁺、CD4⁺/CD8⁺），治疗期间不良反应发生情况，随访12个月期间生存预后情况［无进展生存期（PFS）、总生存期（OS）］。采用独立样本t检验、配对t检验、χ²检验、Fisher确切概率法、Log-rank检验进行统计学分析。结果　观察组客观缓解率和疾病控制率均高于对照组［56.25%（36/64）比37.93%（22/58）、85.94%（55/64）比70.69%（41/58）］（均P<0.05）。治疗后，观察组血清CEA、SCC及CYFRA21-1水平均低于对照组［（14.92±3.51）μg/L比（17.05±4.42）μg/L、（27.64±5.94）μg/L比（30.02±6.67）μg/L、（7.51±2.03）μg/L比（8.64±2.15）μg/L］（均P<0.05）；观察组血清CD3⁺、CD4⁺、CD4⁺/CD8⁺水平均高于对照组［（52.09±5.53）%比（39.97±5.28）%、（48.71±6.35）%比（36.18±5.09）%、1.84±0.31比1.12±0.35］（均P<0.05）。治疗期间，两组不良反应（发热、甲减、瘙痒、白细胞计数降低、转氨酶升高）发生率比较，差异均无统计学意义（均P>0.05）。随访结束，观察组失访2例，对照组失访1例，有效随访率为97.54%（119/122）。观察组和对照组中位PFS分别为9个月、6个月。对照组中位OS为11个月，观察组未达到中位OS。随访12个月时，观察组总生存率高于对照组［69.35%（43/62）比47.37%（27/57）］（P<0.05）。两组PFS、OS比较，差异均有统计学意义（均P<0.05）。结论　替雷利珠单抗联合白蛋白紫杉醇和顺铂治疗老年晚期NSCLC脑转移患者有助于抑制肿瘤标志物表达，调节免疫功能，提高疗效，且安全性较好。

关键词:

非小细胞肺癌, 脑转移, 老年, 白蛋白紫杉醇, 顺铂, 替雷利珠单抗