Pembrolizumab combined with induction chemotherapy and radiotherapy has good clinical efficacy in patients with intermediate and advanced lung squamous cell carcinoma
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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. -
图 1 某男性患者左肺鳞癌(T4N2M0 IIIB期)病理图
病理诊断：(气管镜活检)低分化癌，结合免疫组化结果倾向鳞状细胞癌；免疫组化结果：CK7(3+)，CK 5/6(-), P40(2+), TTF-1(-), NapsinA(-), Syn(-), Ki-67(80%+).
Figure 1. Pathological picture of a male patient with left lung squamous cell carcinoma (T4N2M0 stage IIIB. HE staining, ×100).
图 3 诱导化疗和免疫治疗1周期后胸部CT图(病灶明显缩小)
Figure 3. Chest CT after one cycle of induction chemotherapy and immunotherapy (the focus was significantly reduced).
图 4 诱导化疗和免疫治疗2周期后胸部CT图(病灶较之前缩小，PR)
Figure 4. Chest CT after 2 cycles of induction chemotherapy and immunotherapy (lesions smaller than before, PR).
图 5 治疗2周期后放疗后胸部CT图(SD)
Figure 5. Chest CT (SD) after radiotherapy after 2 cycles of treatment.
图 6 放疗后再进行2周期的诱导化疗和免疫治疗的胸部CT图(SD)
Figure 6. Chest CT (SD) of two cycles of induction chemotherapy and immunotherapy after radiotherapy.
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 
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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.
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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.
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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.
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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
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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.
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