Pembrolizumab combined with induction chemotherapy and radiotherapy has good clinical efficacy in patients with intermediate and advanced lung squamous cell carcinoma
-
摘要:
目的 探究帕博利珠单抗联合诱导化疗、放疗对中晚期肺鳞癌患者临床治疗效果及肺部CT表现的影响。 方法 选取2019年11月~2020年12月本院收治的80例中晚期肺鳞癌患者,采用随机数字表法分为对照组和观察组,40例/组。对照组给予诱导化疗+放疗,观察组在对照组的基础上给予帕博利珠单抗。比较两组临床疗效和肺部CT表现、T淋巴细胞亚群(CD3+、CD4+、CD8+、CD4+/CD8+比值)、血清肿瘤标志物(CYFRA21-1、癌胚抗原、鳞状细胞癌相关抗原)、不良反应及生命质量(健康调查简表)。 结果 观察组客观缓解率和疾病控制率高于对照组(P < 0.05),肺部CT可用于评估患者临床疗效。治疗后,与对照组相比,观察组客观缓解率和疾病控制率更高(P < 0.05),CD3+、CD4+、CD4+/CD8+比值均更高(P < 0.05),CD8+更低(P < 0.05),CYFRA21-1、癌胚抗原、鳞状细胞癌相关抗原水平更低(P < 0.05),健康调查简表各领域评分明显较高(P < 0.05),不良反应总发生率的差异无统计学意义(P>0.05)。 结论 帕博利珠单抗联合诱导化疗、放疗对治疗中晚期肺鳞癌患者具有较好的疗效,改善T淋巴细胞亚群和肿瘤标志物水平,安全性好。 Abstract:Objective To investigate the effect of pembrolizumab combined with induction chemotherapy and radiotherapy on the clinical treatment effect and lung CT findings of patients with intermediate and advanced lung squamous cell carcinoma. Methods A total of 80 patients with intermediate and advanced lung squamous cell carcinoma who were treated in our hospital from November 2019 to December 2020 were selected. They were randomly divided into the control group (n=40) and the observation group (n=40). The control group was given induction chemotherapy + radiotherapy, the observation group was given pembrolizumab on the basis of the control group. The clinical efficacy, lung CT findings, T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ratio), serum tumor markers (CYFRA21-1, CEA, SCC), adverse reactions and quality of life (SF-36) between the two groups were compared. Results The objective response rate and disease control rate of the observation group were significantly higher than those of the control group (P < 0.05). Lung CT can be used to evaluate the clinical efficacy of the patients. Compared with the control group after treatment, the objective response rate and disease control rate of the observation group were significantly higher (P < 0.05). CD4+ and CD4+/CD8+ ratios were significantly higher (P < 0.05), CD8+ was significantly lower (P < 0.05), CYFRA21-1, CEA, and SCC levels were significantly lower (P < 0.05), the scores of SF-36 in various fields were significantly higher (P < 0.05), and the difference of overall incidence of adverse reactions was not statistically significant (P>0.05). Conclusion Pembrolizumab combined with induction chemotherapy and radiotherapy has good efficacy in the treatment of patients with advanced lung squamous cell carcinoma. It improves T lymphocyte subsets and tumor marker levels and has better security. -
表 1 两组一般资料比较
Table 1. Comparison of general data between two groups (n=40)
指标 观察组 对照组 t/χ2 P 性别(n) 0.853 0.356 男 27 23 女 13 17 年龄(岁, Mean±SD) 58.65±10.57 57.37±10.88 0.534 0.595 病灶直径(cm, Mean±SD) 3.57±1.19 3.32±1.06 0.992 0.324 TNM分期(n) 1.270 0.260 Ⅲ期 25 20 Ⅳ期 15 20 表 2 两组临床疗效比较
Table 2. Comparison of clinical efficacy of the two groups[n=40, n(%)]
组別 CR PR SD PD 客观缓解率 疾病控制率 观察组 5(12.50) 20(50.00) 7(17.50) 8(20.00) 25(62.52) 32(80.00) 对照组 3(7.50) 13(32.50) 7(17.50) 17(42.50) 16(40.00) 23(57.50) X2 4.053 4.713 P 0.044 0.030 CR:完全缓解;PR:部分缓解;SD:病变稳定;PD:病变进展. 表 3 两组T淋巴细胞亚群比较
Table 3. Comparison of T lymphocyte subsets between the two groups (n=40, Mean±SD)
组别 CD3+(%) CD4+(%) CD8+(%) CD4+/CD8+比值 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 58.15±5.20 66.29±6.02* 33.05±3.81 38.20±4.11* 31.42±3.54 25.00±4.03* 1.07±0.31 1.53±0.43* 对照组 58.50±5.33 61.05±5.84* 33.42±4.06 35.08±4.62* 30.88±3.62 27.28±3.88* 1.08±0.33 1.29±0.40* t 0.297 3.951 0.420 3.191 0.675 2.578 0.140 2.585 P 0.767 < 0.001 0.675 0.002 0.502 0.012 0.889 0.012 *P < 0.05 vs治疗前. 表 4 两组血清肿瘤标志物比较
Table 4. Comparison of serum tumor markers between the two groups (n=40, Mean±SD)
组別 CYFRA21-1 (ng/mL) CEA(U/mL) SCC(ng/mL) 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 11.05±2.69 8.28±1.72* 11.74±1.26 8.49±0.94* 3.41±0.54 2.09±0.65* 对照组 11.38±2.35 9.85±2.08* 11.89±1.43 9.68±1.11* 3.35±0.66 2.87±0.70* t 0.584 3.679 0.498 5.174 0.445 5.164 P 0.561 < 0.001 0.620 < 0.001 0.658 < 0.001 *P < 0.05 vs治疗前. CYFRA21-1:细胞角蛋白19片段抗原21-1;CEA:癌胚抗原;SCC:鳞状细胞癌相关抗原. 表 5 两组不良反应比较
Table 5. Comparison of adverse reactions between the two groups[n=40, n(%)]
组別 肝功能异常 贫血 白细胞减少 恶心呕吐 乏力 总发生率 观察组 2(5.00) (2.50) 2(5.00) 3(7.50) 1(2.50) 9(22.50) 对照组 (2.50) (2.50) (2.50) 1(2.50) 2(5.00) 6(15.00) X2 0.739 P 0.390 表 6 两组生命质量比较
Table 6. Comparison of quality of life between the two groups (n=40, Mean±SD, score)
领域 治疗前后 观察组 对照组 t P 躯体功能 治疗前 50.26±4.96 50.84±4.81 0.531 0.597 治疗后 65.06±5.49* 57.64土5.22* 6.195 < 0.001 躯体角色 治疗前 48.50±4.79 49.39±5.02 0.811 0.420 治疗后 68.09±6.11* 62.96土5.74* 3.870 < 0.001 身体疼痛 治疗前 53.81±5.85 54.58±5.92 0.585 0.560 治疗后 67.48±6.25* 62.29土6.00* 3.789 < 0.001 总健康状况 治疗前 57.26±5.47 56.31±5.32 0.787 0.433 治疗后 70.33土6.27* 64.89土5.95* 3.980 < 0.001 生命力 治疗前 52.02±5.44 51.27±5.56 0.610 0.544 治疗后 67.19土6.08* 60.12土5.84* 5.304 < 0.001 社会功能 治疗前 51.09±5.10 51.50±5.02 0.362 0.718 治疗后 71.42土6.04* 65.54土5.85* 4.347 < 0.001 情绪角色 治疗前 47.52±5.02 48.47±5.24 0.828 0.410 治疗后 65.82土5.98* 57.95±5.73* 6.010 < 0.001 心理健康 治疗前 55.51±5.74 56.35±5.80 0.651 0.517 治疗后 70.10土6.43* 64.73土6.39* 3.747 < 0.001 *P < 0.05 vs治疗前. -
[1] Majem M, Juan O, Insa A, et al. SEOM clinical guidelines for the treatment of non-small cell lung cancer (2018)[J]. Clin Transl Oncol, 2019, 21(1): 3-17. doi: 10.1007/s12094-018-1978-1 [2] Zhang XP, Han S, Zhou HJ, et al. TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non-small cell lung cancer patients[J]. Mol Carcinog, 2019, 58(5): 767-76. doi: 10.1002/mc.22969 [3] Tian YJ, Liu Q, Wu KJ, et al. Meta-analysis comparing the efficacy of nedaplatin-based regimens between squamous cell and non-squamous cell lung cancers[J]. Oncotarget, 2017, 8(37): 62330-8. doi: 10.18632/oncotarget.17499 [4] 曹子肖, 周丽亚, 刘佳慧, 等. 吉西他滨联合奈达铂治疗晚期肺鳞癌的近期疗效观察[J]. 蚌埠医学院学报, 2021, 46(4): 475-9. https://www.cnki.com.cn/Article/CJFDTOTAL-BANG202104015.htm [5] Brody R, Zhang YD, Ballas M, et al. PD-L1 expression in advanced NSCLC: insights into risk stratification and treatment selection from a systematic literature review[J]. Lung Cancer, 2017, 112: 200-15. doi: 10.1016/j.lungcan.2017.08.005 [6] Tamura H, Ishibashi M, Sunakawa-Kii M, et al. PD-L1-PD-1 pathway in the pathophysiology of multiple myeloma[J]. Cancers, 2020, 12(4): 924. doi: 10.3390/cancers12040924 [7] 王俊松, 吕秀鹏. 卡培他滨、奥沙利铂联合帕博利珠单抗对进展期胃癌的疗效及安全性[J]. 实用药物与临床, 2022, 25(3): 217-20. https://www.cnki.com.cn/Article/CJFDTOTAL-LYLC202203006.htm [8] 陈婧, 高玉华, 马丹丹, 等. 帕博利珠单抗联合培美曲塞、顺铂在食管鳞癌术前新辅助化疗中的效果及对SCCA、CEA、PD-1/PD-L1的影响[J]. 解放军医药杂志, 2021, 33(7): 23-7, 31. doi: 10.3969/j.issn.2095-140X.2021.07.006 [9] 丁婕, 戴旭, 孟宪运, 等. 实体瘤疗效评价标准的研究进展[J]. 中国肿瘤临床与康复, 2015, 22(9): 1150-2. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZK201509053.htm [10] 方积乾. 生存质量测定方法及应用[M]. 北京: 北京医科大学出版社, 2000: 263-267. [11] 郭涛, 宋忠全, 郭桂芳. 帕博利珠单抗治疗伴有轻度特发性间质性肺炎晚期非小细胞肺癌的临床疗效[J]. 中国老年学杂志, 2021, 41(24): 5532-4. doi: 10.3969/j.issn.1005-9202.2021.24.016 [12] 许德颖. 帕博利珠单抗联合放化疗治疗晚期非小细胞肺癌患者的临床疗效与安全性[J]. 实用药物与临床, 2022, 25(3): 232-5. https://www.cnki.com.cn/Article/CJFDTOTAL-LYLC202203009.htm [13] Yu X, Han CN, Su CX. Immunotherapy resistance of lung cancer [J]. Cancer Drug Resist, 2022, 5(1): 114-28. [14] Khoja L, Butler MO, Kang SP, et al. Pembrolizumab[J]. J Immunother Cancer, 2015, 3: 36. doi: 10.1186/s40425-015-0078-9 [15] Ninomiya K, Hotta K. Pembrolizumab for the first-line treatment of non-small cell lung cancer[J]. Expert Opin Biol Ther, 2018, 18(10): 1015-21. doi: 10.1080/14712598.2018.1522300 [16] Zhang CT, Lu ZM, Huang HY. The difference and relationship of CD4 + and CD8 + tumour infiltrating lymphocytes in lung adenocarcinoma[J]. Oncotarget, 2019, 10(13): 1271. doi: 10.18632/oncotarget.26666 [17] 李爱杰, 刘超, 贺科文, 等. 非小细胞肺癌患者外周血淋巴细胞亚群水平检测临床意义[J]. 中华肿瘤防治杂志, 2020, 27(9): 740-4. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL202009013.htm [18] 戴斌, 黄翠萍, 曹喆, 等. PD-1抑制剂对晚期非小细胞肺癌患者T淋巴细胞亚群、NK细胞及抑制性免疫检查点的影响[J]. 中国老年学杂志, 2021, 41(7): 1393-6. doi: 10.3969/j.issn.1005-9202.2021.07.014 [19] 王芸, 王郁阳, 姜曼, 等. 帕博利珠单抗对晚期非小细胞肺癌患者T淋巴细胞亚群的影响及疗效观测[J]. 中国肺癌杂志, 2021, 24(3): 182-7. https://www.cnki.com.cn/Article/CJFDTOTAL-FAIZ202103005.htm [20] 马萍, 陈婧华, 盖云竹. 血清CA153、CYFRA21-1表达与肺鳞状细胞癌化疗效果的关系[J]. 中外医学研究, 2021, 19(12): 174-6. https://www.cnki.com.cn/Article/CJFDTOTAL-YJZY202112065.htm [21] Xie HL, Gong YZ, Kuang JA, et al. The prognostic value of the postoperative serum CEA levels/preoperative serum CEA levels ratio in colorectal cancer patients with high preoperative serum CEA levels[J]. Cancer Manag Res, 2019, 11: 7499-511. doi: 10.2147/CMAR.S213580 [22] Galindo I, Gómez-Morales M, Díaz-Cano I, et al. The value of desmosomal plaque-related markers to distinguish squamous cell carcinoma and adenocarcinoma of the lung[J]. Ups J Med Sci, 2020, 125(1): 19-29. doi: 10.1080/03009734.2019.1692101 [23] 张缜, 张月峰, 王明博, 等. 肺癌患者术后生活质量影响因素的回归分析[J]. 中国卫生统计, 2020, 37(6): 923-5. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWT202006032.htm